Cannabis Grow

Oral bacteria can enter into the systemic circulation through inflamed gingiva and thereby affect peripheral organs and the CNS. In mice, oral administration of Campylobacter jejuni activated visceral sensory nuclei in the brainstem that processed gastro-intestinal sensory information; Porphyromonas gingivalis, an oral pathogen contributing to the development of chronic periodontitis, may be a risk factor for developing amyloid-beta plaques, cognitive impairment, and dementia. Further, exposure to viral or bacterial pathogens upregulates neuronal Ab expression in nontransformed cell culture models and wild-type rat brains, which may represent a naive antimicrobial defense response. Cannabis smoking alters the oral environment and produces numerous chemicals that directly interact with oral bacteria. Some of the chemicals are toxicants and may perturb the oral microbial ecology.In this study, we found that saliva Actinomyces, Veillonella, Megasphaera, and Streptococcus bacteria were increased, and Neisseria bacteria were decreased in cannabis smokers compared to non-smokers. Two Actinomyces species bacteria and one control Neisseria species bacterium were inoculated to the B6 mice via oral inoculation. A. meyeri administration resulted in reduced global mouse activity, macrophage infiltration,trim tray pollen and increased Ab 42 protein production in the brain.

Non-smoking controls were recruited from the Medical University of South Carolina and University of Connecticut by advertisement on the campus and chosen by self-report of non-drug use. Cannabis-smoking individuals with cannabis use disorder were recruited from the Addiction Center at MUSC. This study was approved by MUSC institutional review boards. All participants provided written informed consent. The cannabis smoking cohort included 16 cannabis smokers and 27 non-smoking controls. The cannabis smokers were on current non-injection cannabis use but not on prescription drug and other illicit drug uses identified by chart reviews and urine tests. The clinical characteristics of cannabis smokers were shown in Supplementary Table 1. We conducted a Timeline Follow-back method, a web-based self-administered, to assess frequency and quantity of past 90-day cannabis uses prior to the study visit. Whether the participants used cannabis and the number of joints, blunts, pipes, bowls, vaporizers, spliffs, edibles, or other methods used. If participants shared a joint/blunt/etc. or otherwise did not use a full joint/blunt/etc., partial numbers were reported. Daily gram calculations of THC uses were calculated .Non-smoking controls were recruited from the Medical University of South Carolina and University of Connecticut by advertisement on the campus and chosen by self-report of non-drug use. Cannabis-smoking individuals with cannabis use disorder were recruited from the Addiction Center at MUSC. This study was approved by MUSC institutional review boards. All participants provided written informed consent. The cannabis smoking cohort included 16 cannabis smokers and 27 non-smoking controls. The cannabis smokers were on current non-injection cannabis use but not on prescription drug and other illicit drug uses identified by chart reviews and urine tests. The clinical characteristics of cannabis smokers were shown in Supplementary Table 1.

We conducted a Timeline Follow-back method, a web-based self-administered, to assess frequency and quantity of past 90-day cannabis uses prior to the study visit. Whether the participants used cannabis and the number of joints, blunts, pipes, bowls, vaporizers, spliffs, edibles, or other methods used. If participants shared a joint/blunt/etc. or otherwise did not use a full joint/blunt/etc., partial numbers were reported. Daily gram calculations of THC uses were calculated .For individuals with cannabis use disorder, we assessed exclusionary psychiatric diagnoses using appropriate modules of the MiniInternational Neuropsychiatric Interview, as described in our previous study. Briefly, The M.I.N.I., a brief structured interview, was to assess current Diagnostic and Statistical Manual of Mental Disorders, 5th edition diagnoses. Because the M.I.N.I. only assesses current diagnoses and a more thorough history of substance use is needed, the substance use module of the Structured Clinical Interview for DSM-V was used for substance use disorder diagnosis. Drug screens were performed using the onTrak test cup, an in vitro diagnostic test for the qualitative detection of drug or drug metabolite in the urine. Results of urine screenings were used to substantiate self-reports of cannabis use.The saliva micro-biome was analyzed and compared between cannabis smoking individuals and non-smoking control individuals. We found that cannabis smoking was associated with decreased oral microbial diversity compared to those in the non-smoking control group. The oral microbial communities differed in the two study groups reflected by the b-diversity. Next, we examined the relative abundance of individual bacterial taxa. The phylum Proteobacteria were decreased in cannabis smokers compared with those of non-smoking controls . At the genus level, enrichment of Neisseria was lower in cannabis smokers than in non-smokers; in contrast, Actinomyces, Veillonella, Megasphaera, and Streptococcus were found to increase among cannabis smokers .

At the species level, 36 species were significantly different in cannabis smokers compared to non-smoking controls after adjusting for multiple comparisons , including 16 species that were decreased and 20 species that were increased in cannabis smokers compared to non-smoking controls . Among the taxa that were increased in the saliva of cannabis smokers, five belonged to the Streptococcus genus, and four belonged to the Actinomyces genus. Among the taxa that were enriched in the saliva of non-smoking controls, six belonged to the Neisseria genus . No differences were observed based on quantity of cannabis use or presence of neurological disease history between the heavy users and light users , and between smoked cannabis containing THC and cannabis containing no THC . Nonetheless, the enrichment of A. meyeri was inversely correlated with the age of first cannabis use . To study which taxa may represent the cannabis smoking oral micro-biome, we reanalyzed and compared the saliva micro-biome from tobacco smokers and non-smoker controls from our published data. Consistent with the results from previously published studies, we found increased Streptococcus and decreased Neisseria in the oral micro-biome of tobacco smokers compared with those in non-smoking controls , which was similar to cannabis smokers. However, Actinomyces genus was only increased in cannabis smokers but not in tobacco smokers . To further analyze Actinomyces genus bacteria, we have shown four Actinomyces species bacteria that were significantly increased in cannabis smokers . Only Actinomyces turicensis was increased in tobacco smokers when compared with non-smoker controls . We further analyzed the difference after adjusting for age, sex, and/or alcohol use. All differences between cannabis users and controls identified in the univariate analysis shown in Fig. S1 remained significant after adjusting for sex, age, and alcohol consumption, although P values were attenuated slightly . When comparing tobacco users to controls, only Streptococcus and A. turicensis , but not Neisseria, remained significant after adjusting for sex and age.

Cannabis smokers have shown premalignant lesions in the oral mucosa with surface decay relative to a control group. The smoking and altered micro-biome composition may lead to a compromised mucosal epithelial barrier, which results in the translocation of bacteria or microbial products into circulation. Thus, bacterial fragments or whole bacteria can appear in the blood from translocation and thereby influence the immune system. To study oral microbial translocation in cannabis users, we evaluated the plasma levels of IgG antibody against antigens derived from A. meyeri, A. odontolyticus, and N. elongata. Plasma levels of IgGs against A. meyeri antigens tended to increase in the cannabis smokers compared to controls , while similar levels of IgGs against antigens from the other two bacteria were observed . These results imply that A. meyeri or its antigens may preferentially translocate from the oral mucosa to the circulation in the setting of an altered oral or periodontal environment in cannabis smokers.In a previous study, oral administration of Campylobacter jejuni activated state of neurons in nucleus tractus solitarius and increased c-Fos expression in the hypothalamic paraventricular nucleusas in mice. To determine if cannabis use-associated oral micro-biome affects CNS, we inoculated live A. meyeri, A. odontolyticus, and N. elongata into the oral cavity of C57BL/6 mice. A. meyeri and A. odontolyticus are oral commensal bacteria and were enriched in the oral micro-biome of cannabis smokers found in this study. N. elongata, which was enriched in non-smoking controls , was used as a control. We examined mouse activity through a uniformly cylindrical arena. The behaviors of mice were quantified and shown by global activity, total distance traveled , average speed , and resting time. The behavior of N. elongata-treated mice in the arena was comparable with the PBS-treated mice. However, compared with N. elongata-treated mice, A. meyeri-treated mice exhibited decreases in global activity,trim bin tray distance traveled, and mean speed, as well as increases in resting time . Next, we have evaluated amyloid production in mouse brain tissues as it is a marker of neurodegenerative diseases. Although Ab 40 tended to be increased in A. meyeri-treated mice, there was no statistical difference between any two groups .

Notably, the Ab 42 peptide in the brain from A. meyeri-treated mice was increased significantly compared to the control groups . To validate alterations in oral and gut micro-biome, we collected the samples from oral swab and stool one week after the final oral administration of live bacteria. specific bacteria were quantified using qPCR, and the abundance of each bacterium was normalized by total 16S rDNA. We con- firmed oral inoculated bacteria by qPCR . Notably, both A. odontolyticus and N. elongata, but not A. meyeri, presented in the oral swab of some mice from the PBS group, suggesting A. odontolyticus and N. elongata may be oral commensal micro-biome in mice . A. meyeri did not present in any group except the orally inoculated A. meyeri group. Furthermore, N. elongata presented in the stool samples from some mice after oral inoculation, but was not signififi- cantly elevated compared to the controls; elevation of A. meyeri in stool after oral inoculation was extremely limited . These results indicate that A. meyeri may not be an oral commensal bacterium in B6 mice, but it can colonize well on the surface of the oral cavity during oral inoculation.Long-term heightened systemic inflammation affects neuroin- flammation, and neuroinflammation may result in CNS damage and Ab protein production. To evaluate systemic inflammation after6-month oral bacterial inoculation, we tested plasma levels of 33 cytokines or chemokines in mice. Among these inflammatory markers, only MIP-1a and TNF-a levels were increased in the A. meyeri group compared to the control group . Plasma levels of MIP-1a were also increased in the A. odontolyticus group compared to the control N. elongata group . However, blood levels of the other microbial TLR-downstream proinflammatory cytokines including IL-1b, IL-6, IFN-g, IP-10, MCP-1, and MIP-2 were similar among the four study groups.We analyzed the correlation of A. meyeri, A. odontolyticus, and N. elongata with cytokine levels, and found that N. elongata enrichment in the saliva was directly correlated with levels of IFN-g in the cannabis smokers. However, after FDR adjustment, the p value was not significant.

No correlation was found between plasma cytokine levels and saliva enrichment of A. meyeri or A. odontolyticus. Infiltrating monocyte-derived macrophages in the CNS was related to the progression of neurodegenerative disease pathology. To investigate the potential mechanism of oral A. meyeri-mediated CNS abnormalities, we evaluated myeloid cell migration and infiltration by IHC using mouse brain tissues after oral inoculation of bacteria. Notably, macrophage infiltration was increased in the brain of A. meyeri-treated mice when compared to N. elongata or PBS-treated mice . In in vitro studies, A. meyeri, A. odontolyticus, and LPS significantly enhanced cell transmigration through microporous membranes in human macrophages via the MyD88 cell signaling pathway . Phagocytosis is a major function of antigen-presenting cells. Bacterial products activate antigen-presenting cells and decrease phagocytic capacity. We found that treatment of N. elongata significantly decreased phagocytosis in both human primary monocyte-derived macrophages and THP-1-derived macrophages. However, treatment of Actinomyces species bacteria maintained macrophage phagocytic capacity similar to those of unstimulated cells . Moreover, as expected, A. odontolyticus or N. elongata induced TNF-a, IL-1b, and IL-6 production in human primary monocytes . Unexpectedly, A. meyeri did not activate monocytes to produce TNF-a, IL-1b, and IL-6 .Long-term cannabis users may suffer disturbed brain connectivity, cognitive impairment, and psychological disorders, but the exact mechanisms are not fully understood. In the current study, we found that chronic cannabis use correlated with alterations of several taxa of the oral micro-biome.

Similarly, the former continental-scale meta-analysis of fossil pollen and archeological evidence indicates that the IP was among the last European areas – along with the British Isles and the Scandinavian region – where Cannabis was cultivated, and this occurred during the Roman Empire and the Early Middle Ages . However, these continental-wide analyses include only a few IP sites in their compilations. For example, Clarke and Merlin  mentioned a single, yet representative, site  where Cannabis was submitted to intensive cultivation and retting and used it to propose the arrival of Cannabis to the IP by 600 CE. McPartland et al.  retrieved their Iberian sites from the European Pollen Database  and other internet facilities and considered 10 IP sites, including two from the Balearic Islands . In this way, although the incoming of Cannabis to the IP may be placed within a rather general European context, the precise timing and pathways of arrival, as well as the internal and external dispersal trends, remain largely unknown. Due to the peculiar climatic, biogeographic and cultural features of the IP mentioned above, a thorough survey focused on this specific region to reconstruct Cannabis history is worth attempting. The potential of the IP for providing useful information in this sense is high, as demonstrated by some studies that have recorded relevant historical developments in the drying rack cannabis industry based on pollen analyses of lake sediments. Among them, the most significant examples were found in lakes Estanya and Montcort`es , where hemp was exploited since the Early Middle Ages.

The advantage of these sites is that the amount of Cannabis pollen deposited in the sediments is consistent with local cultivation and/or retting rather than with dispersal from regional and long-distance sources. Indeed, some aerobiological studies have demonstrated that relevant amounts of northAfrican Cannabis pollen can be transported to the southern IP in a few days . Similarly, a recent study of modern sedimentation in Lake Montcort`es  recorded significant percentages of Cannabis pollen, but the parent plant was absent from the region . This long-distance dispersal ability implies that only the presence of this pollen is not sufficient to infer the local occurrence of Cannabis populations. However, this is not the case for Estanya and Montocort`es, as we discuss at following. In the sediments of Lake Estanya, the first appearance of Cannabaceae pollen was recorded ca. 600 CE  during the Early Middle Ages . From then, the record was continuous until the 1990s. Hemp pollen was accompanied by other cultivated plants, such as Olea , Secale  and other undifferentiated cereal pollen. Hemp percentages remained relatively stable  until the 14th century, when they underwent a significant increase of up to 25% around the middle of the 18th century . This increase was interpreted in terms of hemp retting in the lake, coinciding with a local increase in the cultivation of this plant . This was supported by the study of proxies for water quality and non-pollen palynomorphs. This phase coincided with the maximum hemp production in Spain due to the high demand from the Spanish navy . After these dates, hemp pollen decreased abruptly to values below 10% during the 20th century.

The authors attributed this hemp crisis to a general decrease in cultivation due to the depopulation of the area during the first half of the 20th century. The first pollen records of Cannabis pollen in Lake Montcort`es sediments also occurred at approximately 600 CE and coincided with the disappearance of cereals , which indicates a shift in local cultivation practices from cereals to hemp . Further increases in wild grasses and weeds such as Artemisia  and Plantago  are consistent with the expansion of pastures. Hemp pollen experienced three main phases of abundance, separated by two phases of scarcity. The first two phases  were interpreted in terms of low-intensity cultivation/retting to cover local needs for fiber. The third phase, however, was characterized by significantly high abundances  and was difficult to explain in terms of only local consumption . As in Lake Estanya, this phase  was coeval with the maximum development of the Spanish navy and, as a consequence, of hemp cultivation across the entire country. The same abrupt decrease in hemp pollen was recorded at the end of the 19th century, which has been related to the dismantling of the royal navy, the onset of hemp importation from other countries, the substitution of hemp fiber by other materials such as cotton and synthetic fibers, and the decrease in human pressure . The further increase in hemp pollen in the late 20th century may have been due to the renewed interest in hemp, likely favored by EU subsides.The combination of the meta-analysis discussed above  and the case studies of Estanya and Montcort`es may suggest that wild Cannabis reached the IP during the postglacial period  and that cultivated Cannabis entered much later, by 600 CE. Notably, both entries would have proceeded from the north-eastern sector.

However, in the present state of knowledge, it is still premature to confirm these assessments. The lag of sufficient localities also hinders knowing what happened on the IP with Cannabis during the large gap between post-glacial times and the Middle Ages. The development of a thorough database for the IP, as a basis for further meta-analyses, is essential to understand when and how wild and cultivated Cannabis reached the IP, as well as what happened since those times. In addition to the information available from the above reviews and meta-analyses, other sources of information should be accessed. For example, many other sites are available in the compilation by Carri´ on  that have not been included in the former studies. This compilation gathered almost all pollen records available for the IP by the time of publication and is now being updated with new studies developed during the last decade.A number of these studies are not easy to locate, as they are available only in dissertations and local journals. Finally, some studies do not include Cannabis/Humulus pollen in the diagrams due to its scarcity, but the authors have data in their counting sheets and they can be recovered. Therefore, personal contact with palynologists working on the IP is also needed. All these information sources, along with others that may be located further, should be included in a thorough IP-wide study. Epilepsy is a common neurological disorder affecting 0.5–1% of children.

Approximately one-third of people with epilepsy will experience treatment-resistance which is defined as failure of adequate trials of two tolerated, appropriately chosen antiepileptic drugs to achieve seizure-freedom. Children unresponsive to conventional treatments face an increased risk of cognitive, behavioral, and psychosocial dysfunction that can have a negative impact on their health and development. This prognosis has led to strong consumer interest in and uptake of alternative treatments such as artisanal ‘cannabidiol -rich’ products as a way to manage seizures in children with epilepsy. However, such products are typically of unknown quality, composition, and safety, and their use may conceivably pose unpredictable health risks to these children. Despite increasing access to legal pharmaceutical-grade cannabis products globally, many consumers continue to use artisanal cannabis preparations. This may be done for various reasons including lower cost relative to the prescribed product, lack of awareness or knowledge of the patient access pathways, bias against pharmaceutical products, or perceived superior effectiveness and/or tolerability of artisanal products relative to the prescribed products. Artisanal cannabis oils and tinctures are often concentrated to increase the concentrations of active ingredients such as CBD. This, in turn, may result in unusually high levels of residual contaminants in the final product, risking possible toxicity with oral ingestion. The lack of quality control poses potential health risks to individuals via exposure to cannabis contaminated with pesticides, heavy metals, and residual solvents. This would be of particular concern when consumed by children, or immunocompromised or seriously ill adults, and occurs on a long-term basis. With many individuals continuing to self-medicate with artisanal cannabis preparations in Australia and the US, commercial greenhouse supplies contaminants may be unknowingly ingested by many vulnerable individuals suffering chronic illness, including children and adolescents with epilepsy. In a previous study, we collected individual samples of cannabis extracts from families in Australia who were using them to treat their child’s epilepsy, and conducted an analysis of cannabinoid and terpenoid content.

Contrary to family’s expectations, most cannabis products given to children as a way to treat their seizures contained low concentrations of CBD , while delta-9- tetrahydrocannabinol  was present in nearly every sample. To extend on this previous analysis, we further analyzed the samples for the presence of residual solvents, heavy metals, and pesticides, and compared the results to known toxicological standards. In the Australian context, pharmaceutical-grade cannabis products are strictly regulated, federally approved, quality-assured products that are only available on prescription via a medical doctor. All other cannabis products are illegal and unregulated– here referred to as ‘artisanal products’ – which are generally of unknown composition and are typically sourced via the illegal gray or black market.Samples  were collected between May 2016 and November 2017 across New South Wales and Queensland, Australia, from participants in the Paediatric Epilepsy Lambert Initiative Cannabinoid ANalysis  study. A total of 78 cannabis samples were collected from 41 families who were either currently using cannabis products to treat their child’s epilepsy  or who had previously used such products and now stopped . Of these, 37 families provided multiple samples. These included 68 liquid-based samples , six solidbased samples , three plant matter samples, and one crystal/powder-based sample. Aside from two families who had obtained a legal prescription, all other families were accessing unregulated artisanal cannabis preparations of unknown strength, composition, and quality either via local/homemade sources or international online suppliers. The two samples obtained on prescription were included in the contaminant analysis as they were representative of the types of products accessed by families at the time of the study. Samples were stored in a 80 C freezer and had previously undergone two freeze–thaw cycles for:  phytocannabinoid analysis, and terpenoid analysis, as part of the original study protocol. Further information regarding collection methods and the cannabinoid and terpenoid content of samples can be found in our prior publication. All participants provided written informed consent for the original study protocol while consent for the subsequent contaminants sub-analysis was obtained using an opt-out approach. Ethical approval for the secondary protocol and opt-out consent process was obtained from the University of Sydney Human Research Ethics Committee  and the Children’s Health Queensland HREC . Due to the sensitive nature of the information collected in the original study, all cannabis samples were deidentified for confidentiality and recoded to prevent any risk of participant identification. Therefore, information relating to specific cannabis samples  and the child  could not be linked to the contaminant analysis.

The analysis, including detection, identification, and quantification, of four types of heavy metals, 19 types of residual solvents, and 76 types of pesticides  was performed by a National Association of Testing Authorities -accredited analytical chemistry facility . All samples were analyzed using quality-control standards using a 10% replicate approach except those with a small sample volume which were completed in duplicate as a minimum. To account for the variation in sample volumes remaining from prior analyses in the original protocol, a representative sampling approach was chosen. The maximum number of analyses possible on each sample was determined based on volume available, ensuring at least 30 samples per contaminant group. Samples containing >3 g were analyzed for all three categories of possible contaminants; 2.5–3 g for residual solvents and pesticides only; 2.0–2.5 g for pesticides only; 0.7–1.9 g for residual solvents and heavy metals only; 0.6 g for heavy metals only; and <0.5 g for residual solvents only. Using this approach, 51/78 samples were analyzed for heavy metals, 58/78 for residual solvents, and 31/78 for pesticides. Contaminant analysis methods are described in brief in the Supplemental Files.The list of heavy metals and their associated toxicological limits were obtained from the Australian Government Therapeutic Goods Order No. 93 Standard for Medicinal Cannabis for heavy metals.

A placebo-controlled crossover study involving individuals with infrequent use given cannabis ‘edibles’ at different doses found dose-dependent acute impairments in attention, memory and psychomotor performance. Perceptible drug effect onset occurred 30-60 minutes after intake, peaked at 2-5 hours, and lasted eight hours or more . While the cognitive impairments observed were comparable to similar doses of inhaled cannabis the THC-blood concentrations observed were lower than peak concentrations reported in other studies on cannabis inhalation . On this basis, individuals with ‘edibles’ use could have been under existing limits for THC blood level for cannabis-impaired driving, despite their marked impairment being comparable to that from smoking or vaping THC. Furthermore, extending the evidence on the role of different use modes for cannabinoids, the pharmaco-dynamic effect patterns of CBD itself have been observed to be similar to those for THC products, yet generally also vary depending on the use mode/route employed . Moreover, a recent study reported students using cannabis products in multi-modal ways were at greater risk of cannabis-related problems, dependence, and alcohol co-use than those individuals with single-mode use .Systematic reviews suggest that individuals reporting frequent use of cannabis may develop tolerance to the acute effects of THC, especially its effects on memory, executive functioning, and psychomotor impairments, which are less pronounced in individuals with frequent than those with non-frequent use .

Tolerance is generally evident in a blunting effect on impairment, rather than its avoidance; it appears to be a result of neuroadaptation, a down regulation of cannabinoid receptors in response to frequent THC exposure . A recent meta-analysis confirmed a moderating effect of frequent cannabis use on the subjective impairment and psychosislike effects of THC . A double‐blind,pot drying randomized, placebo‐controlled study of the acute effects of cannabis use on neuro-behavioral functioning found that in subjects with occasional use, cannabis-induced alterations in brain functioning were associated with increased subjective intoxication and decreased behavioral performance; conversely, neuroadaptive processes were observed as facilitating reduced responses in individuals with chronic use . Other studies suggest that acute tolerance may be limited to persons with extremely high-intensity patterns of cannabis use . Individuals engaging in frequent cannabis use may also develop tolerance to the protective effects of CBD . Tolerance may lead to increased cannabis intake in order to achieve the desired level of intoxication, thereby increasing the risk of adverse effects. Some adverse neuro-cognitive effects of cannabis on memory, learning and mental state may reverse after a period of abstinence or substantial reductions in use . Reversible down regulation of brain functioning has been reported in animal and human studies, with structural levels returning to those of healthy controls within a few weeks, or even days, of non-exposure . A recent systematic review concluded that abstinence from cannabis use for periods of >72 hours diminished the neurocognitive deficits found in adolescent and young adult PWUC . Other studies have found reversals in key cognitive deficits but observed residual effects on higher-order cognitive functions and related brain networks .

Overall, conditions and measures of related studies vary considerably . In a sample of young cannabis using women, reductions in cannabis use frequency at 3- and 6-months post-baseline were associated with significant reductions in depressive symptoms, with the largest changes for more severe depressive symptoms at baseline . Furthermore, abstaining or reducing the amount of cannabis smoked can reduce respiratory problem symptoms .Key reviews have documented moderately but significantly increased associations between driving under the influence of cannabis and user-drivers’ involvement in MVCs that cause injury or death . Risk ratios may be higher if evidence is limited to drivers with acute impairments in relevant cognitive and psychomotor control functions . Similar risk associations have been confirmed for motorcycle crashes and occupational injuries . Using cannabis together with alcohol increases multi-fold the impairment of driving-relevant performance skills and MVC involvement risk Driving simulator and on-road performance studies confirm that acute cannabis use impairs driving-related reaction, tracking, and psychomotor control, including among youth drivers as a particular high risk group for driving-related adverse events . THC increases self-administration of nicotine in animals, suggesting increases in its rewarding effects . CBD reduces increased attentional bias towards cigarettes in humans who use both drugs, suggesting it may have anti-nicotine addictive properties . Adolescents who co-use tobacco and cannabis report more problems with and dependence on both drugs, consume more alcohol, and experience stronger withdrawal symptoms than those individuals with singular drug use . In large samples of young adults, co-users of cannabis and tobacco reported more intensive use and poorer physical and behavioral functioning than those without co-use ; similarly, among adults, cannabis use has been significantly associated with the initiation of cigarette smoking, smoking persistence, and relapse after cessation.Maternal tobacco co-use has been identified as a confounder for the possible effects of cannabis use on adverse neonatal outcomes, for example birthweight or gestational age , and predicts future use of cannabis and tobacco by offspring .

The concurrent use of cannabis and alcohol can have complex effects . Individuals reporting daily cannabis use who also used alcohol did not differ in brain structure from matched individuals with alcohol-only use; however alcohol co-use is a potential confounder in studies of long-term cannabis-related cognitive function . Concurrent adolescent cannabis and alcohol use may be associated with better neurophysiological and structural brain outcomes than alcohol-only use, but data are limited and effect dynamics uncertain . It is possible that THC exposure may acutely increase the rewarding effects of alcohol and produce quicker and more marked intoxication, and thus lower alcohol use. Co-using individuals may use both drugs more frequently, increasing the risks of co-morbid substance use and mental health problems, and poorer treatment outcomes than those not using both drugs . Comprehensive reviews suggest that frequent cannabis and alcohol co-use by adolescents is associated with greater neuropsychological impairments, adverse health and psycho-social outcomes, such as poorer academic performance and impaired driving. Concurrent use of cannabis and alcohol increases acute impairment, and increases the risk of MVC involvement and other injuries . Concomitant use of alcohol and/or tobacco with cannabis increases the risks of adverse cardiovascular events, including stroke . Interactions between cannabis and other psychotropic drugs, for example, psychostimulants, may negatively influence physical and mental health outcomes . As specifically relevant for prescription drugs, cannabinoids can inhibit the liver and other enzymatic systems, increasing the plasma levels and hence the toxicity of other psychotropic drugs via adverse drug-drug interactions .

Conversely, there may be some health-protective effects for individuals with high-risk use , but research in this area is underdeveloped. Both THC and CBD can produce drug-drug interactions and related adverse events, such as impaired neurological and cardiovascular functioning and infections . They both can interact with tricyclic antidepressants, central nervous system depressants, protease inhibitors, and warfarin therapy .Some reviews have found cannabis smoking to be associated with adverse cardiovascular outcomes such as acute myocardial infarction , arrhythmias, and ischemic attack , while other reviews have questioned the strength of the evidence . A systematic review found that the association with using large doses of THC was stronger for ischemic stroke than for other cardiovascular outcomes . Case studies have reported temporal relationships between cannabis drying smoking and adverse cardiovascular events, but the confounding role of tobacco and alcohol is unclear . While the evidence for cannabis-related cardiovascular outcomes is limited, it appears that THC exposure can exert substantial stress on the cardiovascular system, especially in individuals with novice or occasional use and consequentially limited tolerance to its effects . Systematic reviews have documented acute dose-response effects of cannabis use on tachycardia in young subjects without cardiovascular deficits . Similarly, cannabis smoking has been suggested as a trigger for AMI in young individuals immediately after use . Furthermore, risks for adverse acute cardiovascular events appear to be dose-dependent, and higher in individuals with frequent use of high THC-potency cannabis as well as in older PWUC and in individuals with pre-existing cardiovascular conditions .It is estimated that approximately half or more of the risks of developing substance use disorders is related to genetic susceptibility/heritability . These effects are partly explained by the additive effects of common variants on neurotransmission pathways and other physiological processes that are partially shared between substances . Comprehensive studies suggest a possible role of specific genetic predispositions for cannabis use problems, adverse psychiatric outcomes, and other substance use disorders .

Large genome-wide studies of cannabis dependence have identified independent regions with genome-significant polymorphisms . In a large genome-wide association study, eight independently associated polymorphisms explained a substantial amount of the variance in associations between cannabis use and risks of other SUDs and schizophrenia. Small but significant associations were found between polygenic risk scores for multiple SUDs and select mental health disorders, some indicating that those with a genetic risk for schizophrenia were more vulnerable to CUD than persons pre-disposed for other psychiatric conditions Overall, data suggest that individuals with an immediate or familial history of SUD or schizophrenia and depression are at elevated risk of developing chronic cannabis-related problems. Given the limitations of genetic risk diagnosis, such histories may serve as the best general indicators of increased risk. In those affected by mental health problems the prevalence of cannabis use is commonly elevated and associated with increased disease severity, progression or outcome severity . The causeand-effect dynamics involved between cannabis use, SUD, and mental health problems are complex, including possibly bi-directional relationships. The effects of cannabis may vary in response to other causes, and its use among those with mental health problems may also be a form of self-medication.Cannabis use has traditionally been twice as common in men as women, but the sex ratio of PWUC has substantially narrowed in more recent birth cohorts in many contexts . Fewer women than men, however, engage in intensive cannabis use, and some sex-based and suggestive gender differences in outcomes have been found, although the data may primarily reflect differential exposure levels . There are sex-related biological differences in the ECS and its role in the metabolic and endocrine systems, which may produce sex-based differences in the effects of cannabis on brain structures and functions and on mental health outcomes . Male PWUC develop CUD more often and typically express more problem symptoms than females. A series of double‐blind, placebo‐controlled pharmacodynamic studies comparing the effects of vaporized and oral cannabis use at different doses by sex found overall dose‐related increases in subjective drug effects and cognitive/psychomotor performance, heart rate, and blood-cannabinoid concentrations in female PWUC. Females exhibited greater peak-THC concentrations in blood and subjective effects as well as ratings of “anxious/nervous,” “heart racing,” and “restless” than males, suggesting differential effect profiles .

Women seem to experience greater and more prolonged sedation and psychomotor impairment from cannabis that also may increase their risks of MVC involvement . Female PWUC may have a higher prevalence of anxiety symptoms or disorder and an earlier onset of schizophrenia, although studies of depression outcomes are mixed . Women engaging in cannabis use, overall, may show a ‘telescoping effect’ in which they may more quickly transition from use initiation to CUD or other problems, although these dynamics may also include gendered differentials in social responses; furthermore, some studies suggest that women may experience more severe dependence and withdrawal symptoms . Male PWUC have been found to have twice the prevalence of cannabis-impaired driving as females .Cannabis use is increasing among older adults in North America but there are only very limited data on health outcomes in this specific age group . Human and animal data on ECS upregulation suggest that some age-related decrements may be balanced by neuro-protective effects or improved cognitive function in older PWUC. Reviews have found limited evidence for adverse effects on neuro-cognitive functioning . Systematic reviews of mental and cognitive health among older adult PWUC found only modest reductions in cognitive performance, and were concentrated in individuals with intensive and higher-dose use . A structural MRI study of frequent older-adult PWUC and non-using controls did not find any inter-group differences in in the brain’s total volumes of gray or white matter.

There were many hydroponic lettuce  researches reported , especially, in terms of ecotoxicological testing, lettuce has been recommended by the Environmental Protection Agency of USEPA  and the Food and Drug Administration, USFDA . Modified Hoagland nutrition and 2-fold ozone-treated sludge dilution solutions were used in hydroponic lettuce here, which was simple, rapid and economic. The domestic sludge was treated continuously by ozone until the concentration of fecal Escherichia coli was less than 1000 colony forming units 100 mL-1 , that is the water quality criterion in GB 5084 . The dilution ratio of the ozonetreated domestic sludge in the irrigation was optimized for lettuce growth. This study works on the scientific exploration of vegetable planting fertilized by the low-cost domestic sludge. This experiment was carried out from November 1, 2015 to January 9, 2016 in the greenhouse  of Agro-environmental Protection Institute, Ministry of Agriculture, China over a period of 70 d. Lettuce seeds of the cultivar Dasusheng were used in all experiments. The lettuce seeds were grown in the artificial substrate and irrigated with water. Three weeks later, when the seedlings grew to four or five true leaves, they were transplanted . Plant roots were washed with distilled water before planted. The average temperature is 15.6°C in the greenhouse, and the air relative humidity is 41.3%. And the characteristics of ozone-treated domestic sludge on the lettuce growth improvement in the water cultivation process were investigated.The representative five plants were removed from each hydroponics at 15 d intervals, and the leaf number, plant height, root length, root weight, fresh weight and dry weight were determined, respectively. The plant roots were cut off and weighted in a Thousandth Balance  after the surface water was absorbed by filter paper. The fresh weight was the weight of the whole plant and measured with Thousandth Balance  too. The chlorophyll content was determined directly using the SPAD-502 Plus Portable Chlorophyll Meter .

The soluble sugar was determined by the anthrone colorimetric method, and glucose is used to make the standard curve . One gram of plant samples was ground into homogenate, transferred to 20-mL scale test tube, kept in boiling water for 10 min. After the homogenate was cool, it was filtrated into volumetric flask. Then, 1-mL filtrate was put into 20-mL tube with stopper and mixed with 1 mL water, 0.5 mL anthrone reagent  and 5 mL concentrated sulfuric acid ,cannabis square pot then kept in a boiling water bath for 10 min. At last, optical density value was measured using Spectrophotometer  under the wavelength of 620 nm . The content of ascorbic acid  was determined by 2,6-dichlorophenol titration. A total of 200 g lettuce leaves were crushed and added to the same amount of 2% oxalic acid, then shaked for 5 min. And the solution was fixed to 100 mL with 1% oxalate. Then 10 mL of the above solution was taken and mixed with 10 mL 1% oxalic acid and 1 mL chloroform, then titrated to the end with 2,6-dichlorophenol indophenol dye . The nitrates were determined by Ultraviolet  Spectrophotometry . A total of 0.51 g samples of lettuce leaves were ground into homogenate with some distilled water, then the homogenate was washed into 100-mL volumetric flask with 30 mL distilled water. Another volumetric flask with 30 mL distilled water only was used as control. Then, 5 mL ammonia buffer , 30 mL distilled water, and 0.5 g powdered activated carbon were added into both flasks and mixed well. Subsequently, protein precipitating agent was added, mixed, and filtered after the sample and control flasks were kept still for 20 min. The absorbance was determined by the quartz color dish in the UV Spectrophotometer. The number of fecal E. coli was measured using enzyme substrate method . The sample was incubated at 44.5°C for 24 h, then the number of E. coli was got by UV irradiation. And the Colilert Reagent was provided by IDEXX, UK.Using biomass as a performance determinant, the lettuce under CK treatment showed the best performance, followed by the lettuces of T2, T1, T3 and T4 treatments.

This trend was observed for all of the agronomic traits determined with the exception of root weight. Root weight was followed the order of CK>T2>T3>T1>T4. The lettuce under CK had obvious advantages in biomass growth, however, its stalk was spindling, which might be caused by excessive nitrogen supply, small temperature differences and lower phosphorusus supply. The common nitrogen and phosphorus contents were 49–210 and 15–198 mg L–1, respectively . In this study, the nitrogen content in modified Hoagland nutrient solution was excessive in comparison with the phosphorus content. Using an analysis of variance, the lettuce cultured by modified Hoagland nutrition solution showed a significant advantage over the others cultured by ozone-treated sludge dilution treatments at all dilutions in the leaf number, plant height, fresh weight, and dry weight . Among all the ozone-treated sludge dilution treatments, the T2 was significantly better than the other three treatments  in the leaf number, plant height, root length, fresh weight, and dry weight. Therefore, from the point of view of lettuce agronomic traits, T2 was the most suitable treatment for lettuce growth and development among all ozone-treated sludge dilution solutions. First, the nitrogen and phosphorus contents in T2 dilution were within suitable range. Second, there were some copper  and zinc  in the hydroponics solution. The results also indicated that T1 had excessive Cu and Zn that limited the lettuce growth. It was also reported by other researches . The lettuce biomass results implied that the nutrients in the ozone-treated sludge dilution solutions could improve lettuce growth at low dilutions and inhibit lettuce growth at high concentration applications. This result might be attributed to the favorable buffering of the nutrient solution around plant roots in the low dilutions, which was similar to that in modified Hoagland nutrition solution. On one hand, it was deduced that the release of organic matter during sludge degradation caused a lack of oxygen to the root tissue. On the other hand, the heavy metal contents in T1 solution were higher than those in CK.

In other words, Cu and Zn contents in the nutrition solution of CK were lower than 100 and 200 μg L–1, respectively. The root elongation bioassay was one of the most straightforward test methods used for environmental monitoring in terms of simplicity, rapidity and economy . Nitrogen and phosphorus contents in T1 nutrition solution was higher than those in CK, but the root length of lettuce in T1 was lower than that in CK. The result was caused by the higher heavy metal contents in T1 solution. There was no significant difference between CK and T2 on the root length, however, the dry biomass of CK was higher than that of T2. It was as a result of lower nitrogen content in T2 than in CK. Additionally, high heavy metal concentrations in the sludge were also harmful, resulting in the decrease of root enzyme activity and the inhibition of root growth. The soluble sugar contents in the lettuce cultured with the ozone-treated sludge dilution solutions and the CK nutrition solution was determined . The soluble sugar contents of lettuce leaves in T2 treatment were the greatest, then followed by T3, T4, T1 and CK. According to the ANOVA analysis, the soluble sugar content of lettuce in T2 treatment showed significantly higher than that of other treatments ; while the soluble sugar contents in the T3 treatment showed significantly higher than that of CK, T1 and T4. There was no significant difference for CK, T1 and T4 treatments.As was known to all, chlorophyll absorbed energy from the light, and then used the energy to turn carbon dioxide and water into carbohydrates. The high soluble sugar content of lettuce in T2 may be the result of an optimal sludge concentration causing overall improvements in plant metabolic activity, transport of trace elements and enzyme activity. These improvements could accelerate adenosine tri-phosphate  synthesis and other enzymatic reactions, leading to increased photosynthesis where soluble sugar was the primary by product from this process.

Cu and Zn were the most likely toxicant elements in lettuce when exposed in the sludge dilution solution . The biological toxicity of ozone-treated sludge dilution solution in T1 was presented, which was caused from the higher toxic compounds  . The Cu and Zn contents were over the range of control standards, which resulted in the decrease of soluble sugar contents in T1 when compared with that in T2.The Vc content in lettuce cultured by various ozone-treated sludge dilution solutions and the CK nutrition solution were calculated by ascorbic acid measurements . The Vc content of lettuce in T2 was the highest among all the treatments, then followed by T4, T1, T3 and CK. And the Vc content of lettcue in T2 was significantly higher  than that of other treatments. No significant difference was observed among the T1, T3, and T4 ozone-treated sludge dilution treatments. The trend of Vc was similar to the trend of chlorophyll and soluble sugar contents for all treatments. Vc was especially found in vegetables and fruits and an essential nutritional element for human and cannot be synthesized within the human body. This vitamin must be obtained from external sources such as food. If the Vc storage content in human body was less than 300 mg, some symptoms would appear, such as increased capillary fragility and subcutaneous haemorrhaging to some degree . Therefore, Vc was an important index for lettuce quality evaluation. The Vc content in the lettuce from the T2 treatment was significantly higher than that of other treatments, demonstrating the advantages of the nutritional value in ozone-treated sludge applications when compared to the modified Hoagland nutrient solution.The nitrate contents in the lettuce leaves cultured by the ozone-treated sludge dilution and the CK nutrition solutions were determined. The results demonstrated that the nitrate content in the lettuce leaves under CK was the highest among all the treatments, followed by T1, T2, T3, and T4 treatments .

Based on the ANOVA results, there were significant differences  between CK and the ozone-treated sludge dilution treatments on the nitrate content in lettuce. Among the ozone-treated sludge dilution treatments, nitrate content in T1 showed significantly higher than that in the T2, T3, and T4 treatments . The nitrate contents of the cultured lettuce in the T1, T2, T3 and T4 were 34.3, 53.93, 55.34, and 68.60% lower than that in CK treatment, respectively. Nitrate content is one of the most important indices in vegetable safety evaluation. Normally, trim tray a certain amount of nitrate in vegetables is harmless to human health. However, nitrate can be converted into nitrite by plants, fungi and human gut bacteria, resulting in the formation of compound nitrosamine that is a strong carcinogen . In addition, excessive absorption of nitrate can lead to mental and developmental retardation, low levels of methemoglobin, or even death . According to the requirements of criterion in GB18406.1 , the nitrate content must be below 600 mg kg–1 in fruits and vegetables, 1200 mg kg–1 in root vegetables, and 3000 mg kg–1 in leafy vegetables. Because 80% of the nitrogen in modified Hoagland nutrition solution is nitrate, the cultivated plant will absorb and accumulate excessive nitrate after the ammonium nitrogen is exhausted . While, the plant can utilize ammonium nitrogen directly when cultivated by the ozone-treated sludge dilution solution due to the main nitrogen source of this solution . Thus, the nitrate contents of lettuce treated by the ozonetreated sludge dilution solution satisfied the nitrate limit  in leafy vegetables set by the GB18406.1- 2001 . As shown in Fig. 3-D, nitrate contents in all the treatments of this study were within security scope, and the nitrate contents of lettuce in T1-T4 were significantly lower than that in CK, which indicated that the lettuces cultivated with demestic sludge were security when evaluated with nitrate index only. The result was consisted with the nitrate contents in the nutrition solution, and the nitrate in CK was the highest. However, the leaves of lettuce in T4 are pale green or yellow, which is typical of nitrogen deficiency. Therefore, T2 and T3 were suitable solutions in terms of nitrogen requirements and security of plant.In this hydroponic experiment, we found that 2-fold ozonetreated sludge dilution solution could improve the quality of hydroponic lettuce more compared to the modified Hoagland nutrient solution.

While the federal government still categorizes cannabis as an illicit Schedule 1 substance , states are increasingly legalizing cannabis use, with 18 U.S. states and the District of Columbia legalizing adult recreational cannabis use and 36 states legalizing medical cannabis use as of May 2021 . These states include California, where voters approved medical cannabis use in 1996 and recreational cannabis use in 2016, with retail sales of recreational cannabis beginning on January 1, 2018 . As cannabis legalization spreads, many health professionals are concerned about negative health effects of possible increases in cannabis use , with particular fears focused on potential fetal harms from cannabis use in pregnancy . Studies investigating potential harms from cannabis use in pregnancy have documented a robust association between cannabis smoking and low birth weight . Some studies find increased risk of pre-term birth or small-for-gestational age associated with cannabis use in pregnancy , but others have not found these associations . Some studies have found associations between prenatal cannabis use and adverse neurocognitive outcomes  and increased psychopathology  in exposed children, especially when maternal cannabis use occurred after pregnancy recognition . However, most studies of harms associated with cannabis use in pregnancy suffer from methodological weaknesses, including an inability to adequately control for potential confounders including poverty  and poly-substance use including tobacco . In light of concerns about cannabis use in pregnancy, mobile vertical rack in 2019 the U. S. Surgeon General recommended total abstinence from cannabis for pregnant people .

The American College of Obstetricians and Gynecologists  recommends that prenatal care providers ask all pregnant people about their substance use, including cannabis, and that “women reporting cannabis use should be counseled about concerns regarding potential adverse health consequences of continued use during pregnancy” . However, adherence to these recommendations appears low . A few studies have examined pregnant people’s perspectives on and experiences with cannabis use in pregnancy. These studies have documented that pregnant people are uncertain but concerned about potential risks to their fetus from prenatal cannabis use , and that they seek information on risks and benefits of cannabis use in pregnancy from the internet as well as from friends and family . This research has also found that pregnant people would like to discuss cannabis with their healthcare providers but may be dissuaded due to concerns about being reported to child protective services  and potentially being separated from their newborn . Many pregnant people report receiving no counseling and education on health aspects of prenatal cannabis use from their healthcare providers , even after disclosing cannabis use . Instead, providers may emphasize legal consequences of use during pregnancy, rather than health-related aspects . Most of this research, however, was conducted in states and in time periods where recreational cannabis was illegal . A recent national study focusing on general  contexts found that people who use cannabis were more likely to disclose use to their healthcare providers in states where such use is legal.But research in the U.S. to date has not yet examined patient-provider interactions regarding cannabis use during pregnancy in a context of legalized recreational cannabis.

To fill these gaps, we conducted a qualitative study of people who used cannabis during pregnancy in California after legalization of recreational cannabis, to explore their experiences of their interactions with providers about cannabis. In May-August 2019, we conducted in-depth interviews for a qualitative study that sought to explore perspectives, decision-making, and experiences of pregnant and postpartum Californians who use cannabis regularly, in the context of legal recreational cannabis. This analysis focuses on participants’ experiences disclosing and discussing cannabis use with providers. A group of community advisors with expertise in prenatal care, preterm birth prevention, substance use disorder treatment, and community-informed research helped refine our interview guide, plan and conduct recruitment outreach, and interpret results. Study participants were eligible if they were currently pregnant or had been pregnant within the last year; had used cannabis regularly  in the last year or in the year before their most recent pregnancy; were 18 years or older; lived in California; and were Englishspeaking. Because research has shown that people who use cannabis during pregnancy in the U.S. come from all racial/ethnic groups and socio-economic positions , we aimed to recruit a heterogenous participant group, recruiting via cannabis dispensaries, healthcare providers, and social media. Several cannabis dispensaries in the San Francisco Bay Area posted or distributed study flyers. Providers in prenatal health and substance use disorder treatment clinics also posted flyers and/or referred patients to the study. On Facebook and Instagram, we recruited via local “cannamoms” groups and local cannabis user groups. We tracked demographic details of recruited participants on a spreadsheet and checked regularly to be sure that a range of racial/ethnic groups, socio-economic positions, and recruitment sources were represented. This led us to adjust recruitment after one month: after 9 of our first 14 participants reported that they were referred from a statewide group prenatal parenting program for Black women, we paused further participation from those in this program to ensure that we had a more demographically diverse sample. Interested participants took part in a 15-minute phone call with study staff for eligibility screening, verbal consent, and scheduling, followed later by an in-depth phone interview of up to one hour.

The first author conducted all interviews. A flexible interview guide  allowed us to cover domains relevant to our study questions while also exploring participants’ priorities and diverse experiences. Here, we report on interview domains covering participants’ patterns of cannabis use before and during pregnancy and disclosure and/or discussion of cannabis use in pregnancy with healthcare providers. Participants were given a $50 gift card in remuneration. Interviews were audio-recorded and transcribed verbatim. One participant declined to be recorded; for that interview, we used extensive notes taken during the conversation to inform development of themes, but did not use any direct quotations. We continued recruiting and interviewing until no new themes emerged in our interviews, suggesting we had reached thematic saturation . We conducted coding of transcripts via a two-step process: “chunking” text according to interview domains, and then detailed close coding within domains . We then conducted thematic analysis  of the coded text, using deductive and inductive methods. The first author conducted all coding and led all authors and community advisors in interpretation of results and articulation of major themes, through discussing codes and interview excerpts, followed by revising themes. We selected representative quotes from across the sample to illustrate each theme; the 15 quotes presented here come from 12 different participants reflecting a range of racial/ethnic groups, ages, and educational backgrounds. The study protocol was reviewed and approved by the University of California, San Francisco Institutional Review Board. All participants used cannabis at least weekly before pregnancy; most reported daily cannabis use, vertical grow rack both before and during pregnancy. More than half reported having reduced or stopped cannabis use upon pregnancy recognition. Some reported a mix of reducing and stopping; of these, some stopped using cannabis early in pregnancy but started again later ; others reduced early in pregnancy and then stopped or planned to stop a month or so before their due date.

A few reported that their use stayed about the same in pregnancy as before, or even increased during pregnancy. Most reported using cannabis to ease pregnancy-related symptoms of nausea/vomiting or lack of appetite, pain, or insomnia, or to cope with stress or trauma; some reported using to relax and enjoy themselves with others. This study finds that pregnant people who use cannabis in California continue to report barriers to open discussion of this use with their prenatal providers, despite state legalization of recreational cannabis. While a recent study found that pregnant people do find verbal screening for alcohol, tobacco, and other drugs acceptable and are willing to disclose their substance use to prenatal providers , previous research has found that pregnant people fear that providers’ knowledge of their use will lead to judgment and punishment, particularly reporting to CPS . Consistent with the older body of research, most participants in the current study reported being unwilling to disclose their cannabis use, due to fears of CPS reporting and potential consequences such as parent-child separation. Previous studies have suggested that such fears lead pregnant people who use drugs to physically avoid and/or emotionally disengage from prenatal care . Here, we extend those previous findings by identifying that pregnant people’s fears of being judged and reported to CPS by providers create barriers to comprehensive and compassionate discussions about cannabis use in pregnancy, even in the context of legal recreational cannabis. It is important to note that our participants’ fears of negative repercussions were centered around CPS report for cannabis use during pregnancy, not around the legal status of cannabis use per se. While few people are criminally prosecuted for substance use during pregnancy, about 1 % of all newborns are reported to CPS related to maternal substance use during pregnancy, including cannabis use . In our study, fears of CPS involvement were reported by participants across racial/ethnic groups, but in actuality there are stark racial inequities in this reporting, with providers reporting 4–5 times more Black than white newborns.While legalization of cannabis may reduce some racial inequities imposed by the racist “War on Drugs” , state legalization does not change the federal status of cannabis as a Schedule 1 substance, nor does it necessarily change the CPS reporting policy in the state; further, CPS reporting policies do not necessarily distinguish between legal and illegal substances . California has not changed their CPS reporting policy since legalizing cannabis . Our research suggests legalizing cannabis for recreational purposes does not resolve the barriers that CPS reporting requirements impose on patient-provider discussion of cannabis use in pregnancy. Our finding that few participants reported their providers asking about cannabis echoes previous research finding that providers consider cannabis use in pregnancy to be lower priority to address with patients than other substances used in pregnancy , and that many providers do not respond to pregnant patients’ disclosure of cannabis use . This silence may be sending a health message: our study concords with prior research suggesting that some patients interpret providers’ silence on the topic as an indication that cannabis is safe to use in pregnancy . Provider silence on cannabis use in pregnancy is inconsistent with ACOG-recommended practices and educational messages and may limit opportunities for nuanced and patient-centered discussions about risks and benefits of continued use.

Even when they do occur, though, patient-provider discussions of cannabis may not be nuanced and patient-centered. In our study, participants who discussed cannabis use with their providers reported hearing a wide range of health/risk messages, from endorsement of cannabis use, to recommended harm-reduction strategies, to what they experienced as threats of CPS reports. The spectrum of messages may reflect some providers’ attempts to acknowledge patients’ range of options on cannabis use in pregnancy . However, the inconsistency may also reflect providers’ uncertainty in the face of nascent and sometimes conflicting evidence on health effects of cannabis use in pregnancy . While this study was not designed to examine providers’ motivations for raising the possibility of a CPS report, this study strongly suggests that patients often interpret providers’ discussion of possible CPS report as a threat. Future research should examine providers’ behavior-change philosophies and approaches related to cannabis use in pregnancy, as well as their reasons for and approaches to discussing possible CPS involvement. This work has important implications. First, state-level legalization of cannabis does not address the CPS reporting policies that more commonly punish people who use cannabis during pregnancy. People concerned about pregnant people facing punishment for their cannabis use should focus on changing CPS reporting policies and not only general-population legalization policies. Second, in their committee opinion on cannabis and pregnancy, ACOG included a recommendation that providers inform patients “of the potential ramifications of a positive screen result [for cannabis], including any mandatory reporting requirements” . The findings from this study suggest that this recommendation, as currently phrased, may have unintended consequences, and thus, perhaps should be revised. Further, this study suggests that ACOG’s statement that “Seeking obstetric–gynecologic care should not expose a woman to criminal or civil penalties for marijuana use”  overlooks the realities of widespread CPS reporting policies and practices and the lived experiences and perceptions of pregnant people who use cannabis.

Group differences were tested using Pearson chi-square or t-tests, as appropriate. Differences of in-home smoking prevalence among the four tobacco-use and cannabis-use groups were assessed using predicted probabilities from mixed effects logistic regression models. All models were adjusted for age and sex with country of origin as a random effect to account for variation in sample sizes of each country and to address the possibility of country-specific influence on associations of in-home smoking by cannabis and tobacco use. Odds ratios  comparing cannabis-only users, tobacco-only users, and dual users to non-users were computed separately for in-home cannabis smoking and in-home tobacco smoking. The ORs for in-home cannabis smoking and in-home tobacco smoking were visually compared by observing non-overlapping 95% confidence intervals. Statistical differences in the ORs were assessed using generalized estimating equations by implementing the methods outlined by Horton & Fitzmaurice . To address possible confounding by participant-level characteristics and country level characteristics , ORs were computed from models that additionally adjusted for clubbing frequency, drinking frequency, past year drug use, ploy-drug use, area of residence, and country as a fixed and random effect. Logistic regression models were then repeated for each included country to illustrate country-specific differences of in-home smoking among the four mutually exclusive cannabis- and tobacco-use groups. All statistical tests were two-tailed with an alpha of 0.05. Data analysis was performed using R . Global trends in the decriminalization and legalization of cannabis use should prompt increased research that seeks to identify and constrain harm and improve public health.

In this large convenience sample of people from 17 countries who used at least one psychoactive drug in the past year, past-year in-home cannabis smoking was slightly more prevalent than past-year in-home tobacco smoking in the overall sample. Approximately 80% of current cannabis-only users reported that cannabis grow set up was smoked in their home while in-home tobacco smoking took place in the residences of 68% of current tobacco-only users. Overall past-year rates of in-home smoking were high among current users of both cannabis and tobacco, and in these groups, in-home cannabis smoke was more prevalent than in-home tobacco smoke. Taken together, these results support our hypothesis that in-home cannabis smoking would be higher than in-home tobacco smoking. Since this is the first study we are aware of that measured the behaviors of in-home cannabis and tobacco smoking, there are no studies to which we can directly compare our results. From studies that focused on household rules, evidence from a convenience sample of US Facebook users reported that of the 54% of respondents who allowed cannabis use on their property, 71% allowed cannabis smoking inside their home; unfortunately, rates of in home tobacco smoking were not available . Another study, among US university students, reported that in-home cannabis use was allowed by 36% of tobacco smokers and 59% of cannabis smokers while in-home tobacco use was allowed by 25% of tobacco smokers and 36% of cannabis smokers . In our study, the generally higher rates among US respondents  could be attributed to our assessment of home smoking behavior rather than home smoking policy. They could also be attributed to selection bias from studying self-selected sentinel drug users, though a recent study showed that the age and sex distributions of GDS respondents who use cannabis were similar to probability-based samples in the three countries studied—Australia, Switzerland, and the US . The high rates might also be partly the result of our yes/no inquiry about past-year in-home smoking, which could include rare instances of the behavior that are not representative of usual behavioral patterns.In a recent cross sectional study in Australia, Canada, England, and the United States, 73.6%, 78.3%, 65.5%, and 60.8% of respondents, respectively, endorsed cannabis smoking as less harmful than cigarette smoking .

Decades of tobacco control campaigns and policy likely increased the perceived harm of tobacco smoke, contributing to the lower rates of in-home tobacco use. If true, results from this study suggest that it may be time to develop similar campaigns and policy to correct perceptions of harm of cannabis smoke. This study underscores the importance of studying in-home cannabis smoking, which occurs at a higher rate than in-home tobacco smoking; however, more research is needed. Cannabis users comprise a sizeable population, both in absolute and relative terms, and with cannabis laws becoming more liberal, the number of users is rising. A major public health goal for future studies is to identify how often in-home cannabis smoking occurs in the general public and in high-use populations. Knowing the rates in the overall population will reveal the full scope of the behavior while understanding rates in high-use groups will quantify the behavior among those who have the most to gain from intervention. Obtaining these prevalence data will inform interventions to eliminate in-home smoking and will encourage further research, including the identification of public health messages designed to prevent in-home smoking  and research on the health consequences of firsthand, secondhand, and third hand cannabis smoke exposure. As with all studies, results of the present analysis should be viewed considering the strengths and limitations of the methods used. While we included data from 107,274 men and women from 17 countries, the data were collected using anonymized web-based surveys specifically targeted toward those who use drugs through advertisements on social media and drug-scene-related media outlets. While non-probability based sampling and self-selection bias prevent generalizable estimates of prevalence , the inferences that were presented comparing in-home tobacco and cannabis smoking by use-status are expected to have significantly less bias since it is unlikely that the primary prerequisite for selection bias  was present. In the Introduction, we referenced online information on tobacco and cannabis control policies that highlight significant variance in the type and implementation of policies across countries. To our knowledge, no study has attempted to quantify the impact of such regulatory differences on the in-home use of cannabis and tobacco, an investigation that was beyond the scope of the present study. However, the presence and diversity of public policies toward both substances should be considered when interpreting our findings.

To reduce bias related to confounding by participant-level characteristics and by country-level characteristics such as regulatory policies, our models statistically controlled for several potential confounders, and included country as a fixed and random effect. Future investigations of how tobacco and cannabis control policies impact in-home smoking are warranted, especially studies that explore how legalized cannabis use, with and without legalized outdoor use, impacts in-home use and subsequent SHS and THS exposure. The self-report origin of our cannabis and tobacco use status and in-home smoking status is also a limitation, although the GDS is a well-respected entity among the drug-using community and is known for preserving anonymity, making it more likely to elicit accurate responses. We were unable to study usual in-home smoking patterns including the frequency of in-home smoking or household composition because we did not collect usable data on these important factors—future studies should capture more detailed data. As a result, our estimates likely overestimate problematic in-home smoking, although this is not expected to greatly bias results since the overestimation is likely non-differential—i.e., similar for both in-home cannabis and in-home tobacco smoking. Transmission of severe acute respiratory syndrome coronavirus 2 , the virus responsible for causing coronavirus disease 2019 , has led to unprecedented morbidity and mortality across the U.S. . Risk factors for COVID-19-relatedsevere illness resulting in possible hospitalization include: active or former smoking status and/or having pre-existing comorbidities or an immunocompromised status . Combustible and non-combustible tobacco users are vulnerable to clinical morbidities, including impaired pulmonary function and respiratory illnesses . Research suggests combustible smoking or vaping cannabis is associated with respiratory-related symptoms and disease . Additionally, vaping nicotine, flavorings, and/or tetrahydrocannabinol  products may place individuals at increased risk for COVID-19- related symptomatology and illness due to impairment of normal pulmonary defenses to inhaled viral pathogens . Smoking, and possibly e-cigarette use, can upregulate the angiotensin-converting enzyme-2 receptor, which is the receptor for SARS-CoV-2 . However, human research studies are lacking on concurrent e-cigarette and cannabis use and COVID-19-related health outcomes. Research has linked respiratory symptoms or disease with adult current e-cigarette use , current cannabis combustible smoking and vaping , and lifetime e-cigarette and cannabis use . College student ecigarette use and outdoor cannabis grow smoking and vaping reached historical highs between 2017 and 2019 . Currently, 22% and 14% of students report past 30-day nicotine and cannabis vaping, respectively . Over one-in-four students report current cannabis use including other routes of administration , with 1-in-17 reporting daily cannabis use. While current dual use of e-cigarettes and combustible cigarettes has been associated with increased risk of COVID-19 symptoms and diagnosis among 13–24-year-olds , less is known about COVID-19-related risks associated with concurrent e-cigarette and cannabis use.

Given the high prevalence of e-cigarette and cannabis use among college students , research is needed to assess the associations between concurrent use and COVID-19-related outcomes. This investigation assessed whether current e-cigarette and cannabis use was associated with COVID-19 symptomatology, testing, and diagnosis among college student current e-cigarette users. We hypothesized concurrent users of e-cigarettes and cannabis would be at increased odds of experiencing COVID-19 symptoms and having a prior positive COVID- 19 diagnosis compared with exclusive e-cigarette users. Additionally, we assessed whether frequency of e-cigarette and cannabis use was associated with COVID-19 symptoms, testing, and diagnosis. We hypothesized that when compared to infrequent exclusive e-cigarette users, intermediate or daily exclusive e-cigarette users as well as infrequent, intermediate, and frequent concurrent e-cigarette and cannabis users would be at increased odds of reporting COVID-19 symptoms and diagnosis. Based on COVID-19 random selection testing policies at each university during the study period, we posited there would be no difference in COVID-19 testing between the exclusive e-cigarette and concurrent use groups. Data are from a cross-sectional, online survey conducted October December 2020. Participants were college students  ages 18–26 years from four geographically diverse, large U.S. public universities  who reported current ecigarette use. Institutional review boards  at each university independently vetted and approved all study procedures by November 2020; data collection occurred after respective IRB approval. Students at each university had the option to complete their coursework online, in person, or a hybrid model. Students residing in university housing/ residences were allowed to remain on each of the respective campuses during the data collection period. COVID-19 testing programs at each of the four respective campuses were similar and required randomly selected students to undergo testing. Eligible participants were recruited by disseminating emails via campus-wide listservs and undergraduate and graduate course listservs. Participant recruitment strategically took place at least over one month into the fall semester due to the study’s aim of capturing past 30-day behavior during the academic year. Solicitations sought students between the ages of 18–26 who “vape or use e-cigarettes” and were currently on campus. The recruitment email included a website link to a survey hosted on Qualtrics , and stated the estimated completion time was 10 minutes. Potential participants were provided with a research information sheet which they needed to acknowledge prior to proceeding to the survey.

The information sheet reinforced the recruitment email’s information . Response rates were not available due to recruitment strategies employed. However, sample size calculations using a 95% confidence interval , 100,000-population size, and a conservative 50–50 split considering the population is relatively varied , assert a minimum of 383 completed surveys were needed to have sufficient power for statistical analysis. To assess cannabis use, students were asked, “During the past 30 days, how many times did you use marijuana?” Response options were: 0, 1–2, 3–9, 10–19, 20–39, and 40 or more times. We classified the sample of current e-cigarette users based on their current cannabis use response as: exclusive e-cigarette users  and concurrent ecigarette and cannabis users . To assess frequency of use patterns, we combined responses from the item on how many times students used cannabis with the item on how many days students used e-cigarettes in the past 30 days .

THC is a partial agonist at CB1 receptors, and frequent cannabis use results in downregulation of CB1 receptors with a potential to reverse with abstinence . Another main cannabinoid is cannabidiol , which is non-intoxicating . CBD has a broad range of pharmacological actions, including inhibiting the reuptake and hydrolysis of anandamide as well as multiple receptor mechanisms . The receptor mechanisms include negative allosteric modulation of CB1 receptor, partial agonist or inverse agonist action on CB2 receptor, and agonist action on transient receptor potential vanilloid 1 and serotonin 5-HT1A receptor , all of which are thought to lie behind CBD’s effects in reducing drug reward and addiction in preclinical studies . Broadly speaking, cannabis products can be divided into four categories: high-THC-concentration/sinsemilla , herbal , hash/ resin , and very high-THC cannabis concentrates In the past two decades, dramatic increases in THC concentration in cannabis products have been reported across Europe  and the U.S. . For example, a large study from the U.S. found a general increase in THC concentration in seized cannabis plant material from about 4% in 1995 to about 12 % in 2014 , and a comprehensive study from France found a dramatic increase in THC concentration in seized cannabis resin from 10 % in 2009 to 23 % in 2016 . In line with these findings, a recent study found an alarming 3-fold increase in THC concentration in seized cannabis resin in Denmark from 8% in 2000 to 25 % in 2017 , which represents the highest concentration throughout Europe . During the same period several studies indicate that CBD concentrations have remained stable or even decreased; in the studies from France and Denmark, CBD concentration remained stable at around 4% and 6% .

This development is highly concerning, as emerging studies show that cannabis products with high THC levels and low CBD levels may have more detrimental effects on cognitive function and mental health among both young and adult users , including higher risk of cannabis-induced psychosis ,vertical grow system impairments in learning and memory , and poorer addiction outcomes . Increasing THC levels have also been linked with increases in admission to CUD treatment in Europe .For example, 18 % of youth aged 15–24 in Europe report using cannabis the past year compared to 7 % of 25− 64 year old’s . In the U.S., about 25 % of adolescents report cannabis use by age 14, and recently rates of cannabis use have started to approximate adolescent alcohol use patterns with half of adolescents now using cannabis by age 18 . Notably, the percentage of lifetime cannabis using adolescents who report frequent use  are at the highest level in recent decades , reflecting a three-fold increase from the lowest reported levels in 1990–1991. Rates of CUD peak during adolescence and emerging adulthood, and the global burden of disease related to cannabis use peaks in emerging adulthood. Individuals who initiate cannabis use during adolescence experience more adverse and long-lasting cannabis-related harms . About 30 % transition into CUD , and there is an increased risk of other substance use disorders  later in life . Particularly among youth, frequent cannabis use is linked with a wide range of mental health disorders, health risks, and poor psychosocial outcomes, including low life satisfaction, school dropout, lower educational and occupational achievements, behavioral and legal problems, accidents/injuries, sexually transmitted infections, and psychotic disorders during adulthood . The increased risk of adverse outcomes associated with frequent cannabis use among youth is related to the nature of the developing brain and the role of the endocannabinoid system in the neurodevelopmental maturation during adolescence . The brain continues to develop from the prenatal period through childhood and adolescence until the beginning/mid 20 s . During these developmental periods, the brain is believed to be more vulnerable to the adverse effects of neurotoxins, such as regular exposure to cannabis.

This means that the health impact and effects of cannabis, stemming from the increase in cannabis potency may pose unique risks for youth, because THC is likely to interfere with the neurodevelopmental processes influenced by the endocannabinoid system . Related to this, a study of regular cannabis users and matched controls , found that cannabis use was associated with impaired axonal connectivity in the fimbria of the hippocampus and the precuneus , and that early age of onset of regular use was associated with more severe microstructural white matter alteration. Additionally, a multisite longitudinal study in Europe found that cannabis use was associated with accelerated age-related cortical thinning between the ages of 14 and 19, predominantly in prefrontal regions with a high density of CB1 receptors . Further, studies examining response inhibition have shown that adolescents engaged in cannabis use require more neural resources to perform at the same level as non-using adolescents  , or perform worse . However, longitudinal studies are required to determine if these differences are directly related to THC exposure or whether they may  predispose individuals for developing CUD. In the only randomized, placebo-controlled study of cannabis administration in adolescents and adults to date , adolescents experienced heightened impairment of response inhibition and wanting more cannabis, alongside blunted subjective effects and memory impairment compared to adults. Preventing and intervening in the neurocognitive and health sequelae of early or frequent cannabis use is complex, and involves physical, psychological, medical, and cultural considerations. With regard to youth cannabis use, it is important to first consider the ways in which adolescents and emerging adults are developmentally distinct from adults in ways that have historically posed challenges to substance use prevention and treatment interventions in general . One barrier to preventing the onset and escalation of adolescent cannabis use is that across cultural contexts, experimentation with substances such as alcohol and cannabis often falls in line with cultural expectations, and is perceived as socially acceptable by the youth . However, the cultural and social context that influence an early onset of cannabis use may also have adverse neurocognitive implications for later brain and behavior function and ability . As summarized in Silvers et al. , adolescence and emerging adulthood is a period with unique neuro developmental tasks that underscore major contrasts from adulthood: myriad pubertal changes, rapidly developing cognitive skills, an emergence of self-identity, and prominent changes in the social landscape.

Accordingly, adolescent cognitive skills are also more directly tied and embedded in, and thus strongly impacted by, the socioemotional context and the broader ability to engage in self-regulatory cognitive strategies  is only emerging and is markedly different from adults . Because the ability for abstract reasoning and the capacity for purposeful and planful behavior is also in a developmental neurocognitive phase, this may subsequently impact the ability to participate meaningfully in established empirically supported behavioral treatment paradigms for substance use that have historically been designed for adults and largely validated with adult samples . Exploring personal identity and a heightened sense of self also demarcates and differentiates the neurodevelopmental period of adolescence and emerging adulthood, and the formation of self-identity is itself contingent upon increased self-awareness and self-monitoring . Unique to this developmental period, enhanced self-focus and social attunement with the environment may motivate youth to use substances to improve social standing, particularly within peer contexts . In contrast to adults, adolescents may also be more likely to take risks in the presence of their peers such that risk taking in social contexts heightens the potential reward value. Of note, this penchant toward enhanced risk taking has now not only been examined as a potential risk factor, but also as a likely resilience factor, as adolescents also have an enhanced capacity to engage in prosocial “risks” when in peer contexts . Peer influence is thus a powerful motivator for both risk taking and prosocial behaviors, highlighting the significance of addressing peer interactions in adolescent prevention and treatment interventions. These central facets of neurodevelopment in adolescence and emerging adulthood highlight key contextual distinctions between youth and adult cannabis users; the assumption that adult substance prevention and treatment models work equally well for youth is itself a barrier to developing novel approaches. Another major challenge in addressing the significant public health issue that cannabis use presents for youth is that most youth who engage in frequent cannabis use do not seek or receive prevention and treatment interventions , even after years of harmful use and related negative health sequalae; on average, cannabis users have more than 10 years of near-daily use and more than 6 attempts at quitting, prior to seeking and/or receiving treatment . However, despite the high clinical importance, research on barriers to prevention and treatment interventions among youth with frequent cannabis use is surprisingly scarce, although some studies suggest that central barriers for seeking timely help involve social stigma, mobile grow systems an overall desire to be self-reliant, believing intervention is not needed, or presuming that programs will be ineffective .

Additional complicating factors involve the increasing ease of access to cannabis, particularly in regions with permissive cannabis legislation , which has been directly tied to increases in youth cannabis use , perceiving cannabis use as harmless , and increasing social acceptance of cannabis use among peers . Moreover, positive associations with cannabis  coupled with limited experience of, and anticipation for, negative consequences among adolescents and emerging adults, mean that this age group might not have a sensation of urgency to seek intervention either on the personal side  or on the social side. Related, once successfully engaged in prevention and treatment interventions for CUD, a significant challenge is retaining youth in the intervention . Further, the recent National Academies on Cannabis report  also underscored the additional challenge of potential increase in other substance use. Taken together, to reach and help youth with/at-risk of developing CUD at an earlier stage, there is a dire need to develop and test new prevention and treatment interventions that are articulated specifically for this important neurodevelopmental population. Psychosocial interventions for cannabis use can be employed at different stages prior to and into the development of CUD and have been assessed both in non-treatment seeking youth and in youth enrolled in treatment. In particular, an important avenue for circumventing treatment barriers and reaching non-treatment seekers, and maximizing prevention and treatment impact, is via brief, early evidence-based interventions that are non-judgmental and affirming . Motivational interviewing  is very well-suited to this end, because it is, by definition, non-judgmental, strength-based, affirming, empathic, and bolsters motivation for change , and has shown to be highly acceptable and feasible among young cannabis users . Prior studies have found that 2 sessions of MI can successfully reach and engage non-treatment-seeking young cannabis users and reduce cannabis use and related symptoms . However, compared to adults, effects of MI have generally been less impactful among youth . Combining brief, evidence-based psychological interventions like MI with safe and effective pharmacological treatment may represent an important avenue for reaching and engaging non-treatment seeking youth, helping them reduce or quit cannabis use, and facilitate a healthier trajectory. Multiple psychosocial interventions have been investigated for adolescents and emerging adults enrolled in CUD treatment, however these interventions have typically been developed for use in adult  populations and not for cannabis as the primary problem drug .

Several reviews provide in-depth details on the nature and efficacy of each intervention approach , but examples include that the combination of MI and cognitive behavioral therapy  is associated with reduced cannabis use in adolescents with CUD. Typically, MI is employed over one or two sessions initially, in order to increase motivation to stop using cannabis and enhance ambivalence towards reducing use. This is followed by several sessions of CBT, with the aim of introducing coping skills that can be used in real-life settings and include devising plans for specific high-risk situations and developing problem solving skills. Recent studies have also shown that adding vouchers or monetary incentives for not using cannabis  to weekly MI + CBT in youth has been associated with increased abstinence from cannabis  and increased treatment retention  compared to weekly MI + CBT alone. Finally, some studies on multidimensional family therapy , an approach that involves both the adolescent and the family member, have found that MDFT has comparable efficacy to CBT over 5-6 months of treatment, with evidence of increased treatment acceptability , and that a 6-month programme has been associated with good retention as well as reduced cannabis dependence compared to individual psychotherapy .

The legalisation of large-scale adult non-medical recreational cannabis use and supply in 15 U.S. States, Canada and Uruguay has reignited the international debate about the best policy approach to cannabis , 2020; Kilmer, 2019. Citizen initiated referenda have been the primary mechanism by which medicinal and recreational cannabis use has been legalised in U.S states over recent decades . Given the politically divisive nature of the cannabis law reform debate, politicians in other jurisdictions may well choose to resolve the issue via referendum in the future, allowing citizens to directly state their preferences and thereby legitimise any policy change .In New Zealand, the Green political party made holding a national referendum on the legal status on recreational cannabis use a condition of their support for the 2017 Labour and New Zealand First coalition government . The resulting 2020 New Zealand cannabis referendum was a world first in the sense that it was a national vote, as opposed to the previous U.S. state referenda, and involved voting on a detailed legislative bill , rather than a general question on whether cannabis should be legal or not . The New Zealand cannabis referendum was narrowly defeated, with 48.4% voting to support compared to 50.7% voting to oppose the CLCB  . Along with the notable successes, referenda to legalise non-medical recreational cannabis use and supply have also periodically failed in some U.S. states . The narrow defeat of the New Zealand referendum raises important questions about what factors were responsible for the lack of voter support for the CLCB and cannabis legalization in general. Understanding these factors could inform future advocacy and referendum campaigns for cannabis legalisation in other jurisdictions. The existing literature has identified three main determinants of voting behaviour: self-interest , moral values , and political party identification. Self-interest would predict that users of recreational and medicinal cannabis should support legalisation to remove the risk of arrest to themselves and to reduce social stigma related to their cannabis use.

If voting is influenced by moral values, those who view cannabis use as morally wrong should be more likely vote against legalisation, as should those who believe cannabis consumption to be a significant health risk and social harm. If, after controlling for a range of demographic, behavioural and attitude factors, political party affiliation remains a significant predictor of voting intentions related to cannabis legalisation, then this would suggest that similarity in voting amongst members of a party is not only related to shared views of the world, but also by the social identity generated by association with a particular political group .In the United States, national support for cannabis grow racks legalisation has grown steadily over recent decades, from only 12% in 1969 to 64% in 2017 . Poll support for cannabis legalisation in the U.S. is higher amongst men, younger age cohorts, those who have ever tried cannabis, and left leaning voters . Multivariate modelling has found the strongest predictors of support for cannabis legalisation amongst 18–34 year olds in the U.S. are perceptions that cannabis is less harmful than cigarettes and having used cannabis in the past month . Male gender remains a significant predictor of support for cannabis legalisation amongst this age group, while age, ethnicity, education, and current social smoking were no longer significant after controlling for other variables . Multivariate analysis of state-wide data from Michigan  found left of centre or centrist political views, past year cannabis use, and lifetime cannabis use were all predictors of supporting cannabis legalisation . Alternatively, older respondents, women, and those who perceived cannabis use to be risky were found less likely to support legalisation . Multivariate analysis of U.S. national data found women with greater religiosity less likely to support cannabis legalisation after controlling for a range of variables, suggesting cannabis law reform has an important moral dimension . Schnabel and Sevell  come to a similar conclusion from analysing U.S. national poll data from 1988 to 2014, arguing that increasing support for both cannabis legalisation and same sex marriage over recent decades reflflects the growing acceptance of these issues as matters of individual autonomy rather than matters for government control.

In New Zealand, public polling on cannabis law reform has been conducted on a fairly regular basis for the past two decades, with as many as 45 polls conducted on the issue since the beginning of the Millennium . These polls have generally found very high levels of support for medicinal cannabis reform, with around two thirds of respondents supporting some kind of decriminalisation involving civil fines, and only a minority supporting full legalisation of recreational use . Since 2018, public polling has focused more specifically on the question of support for the legalisation of recreational cannabis use, reflecting the coalition government’s announcement of the referendum on the issue. Thirteen polls were conducted in the year of the referendum vote, of which seven found a majority in favour of legalisation, five a majority against, and one reported an even result . A poll of Māori  in the same year found 75% in favour of legalisation . Basic cross tabulations of New Zealand poll results have found higher support for cannabis legalisation amongst men, younger age cohorts, Māori, and Green Party and Labour Party voters, and alternatively, lower support amongst National voters and those aged over 65 years . The only published multivariate modelling of poll support for cannabis legalisation in New Zealand to date found significant predictors of positive support for cannabis law reform were prior experience of using cannabis and other illegal drugs, a history of depression, scoring higher on a novelty-seeking measure, Māori ethnicity, parental drug use, and higher educational achievement . Predictors of more negative attitudes to reform amongst this longitudinal sample were female gender and having dependent children . As acknowledged by the authors, the sample was limited to a single birth cohort of 40-year olds, interviewing was completed prior to the announcement of the cannabis referendum, and the reforms presented to respondents referred to a range of possible liberalisation initiatives, including legalising medicinal cannabis, decriminalisation, permitting home growing, age restrictions and full commercial legalisation . The New Zealand cannabis legalisation referendum  proposed a strictly regulated legal cannabis market that most closely resembled the Canadian approach to cannabis legalisation . The CLCB would restrict the purchase and use of cannabis to those aged 20 years or older ; a daily purchase and possession limit of 14 gs; sales from licensed physical stores only ; separate licensed consumption premises; no advertising or promotion; a personal home cultivation limit of two plants ; social sharing of up to 14 g of cannabis; no industry sponsorship or free giveaways; limits on the potency of products ; an excise tax based on the THC potency and weight of products; mandatory inclusion of health warnings on products and displayed at licensed premises; and no public consumption or sale with alcohol, tobacco, food or any other product . Due to conflicting views on cannabis law reform from within the coalition government partners, it was agreed the government would only run what was termed a “signposting” campaign directing voters to the referendum website  where neutral information would be available, rather than actively campaigning for the passage of the CLCB .

The referendum site included short bullet point summaries and a complete version of the CLCB . A brochure on the referendum directing voters to the referendum website was also posted to all enroled voters . The coalition government purposively left advocacy concerning the relative merits of the CLCB and wider legalisation to interest groups and the media . In the months preceding the referendum vote, proand anti-legalisation interests funded substantial traditional and social media advocacy campaigns, and there was also considerable media coverage of the issue and a series of town hall style public debates . While a number of public polls were conducted to track voter support for the CLCB in the months preceding the referendum, there has been no analysis of what underlying factors explained voter support or opposition to the CLCB.Our models found that age, ethnicity, education, religiosity and even cannabis use experience were no longer statistically significant predictors of support for the CLCB once we controlled for perceptions of the health risk of cannabis use, experience with and support for medicinal cannabis use, moral views of cannabis use, and actual reading of the CLCB. This suggests support for recreational cannabis legalisation in New Zealand is not based on broad demographic characteristics, but rather specific views about the moral acceptability, health risk and medicinal benefits of cannabis use, and deep-rooted ideological perspectives. Elder and Greene  found that religiosity played an important role in women’s opposition to cannabis legalisation after controlling for a range of variables, suggesting that cannabis legalisation has a prominent moral dimension for some people, similar to issues such as access to pornography and abortion. Elder and Greene  included measures of religious commitment in their models, that is frequency of religious attendance  and describing oneself as “born again” Christian. Our measure of religiosity covered a broad range of spiritual and religious beliefs, some of which may not hold as strong anti-drug prescriptions as evangelical Christians in the U.S. In addition, our religiosity variable was a simple yes/no response, and thus may not have captured the intensity of religious belief as Elder and Greene‘s  measures.Experience of the medicinal benefits of cannabis has also been found to be one of the leading reasons for supporting recreational cannabis legalisation in the U.S. .

A recent survey of medicinal cannabis grow system users in New Zealand found the overwhelming majority reported positive therapeutic benefits from their cannabis use , and this positive experience is likely to mean this group has fewer qualms about supporting recreational cannabis legalisation. During the referendum, opponents of the CLCB strongly objected to a pro-campaign promotion that referred to the CLCB as a means to obtain greater access to cannabis for medicinal purposes, pointing out that medicinal use had already been recently legalised in New Zealand [via the Misuse of Drugs  Regulations 2019. In contrast, pro-legalisation campaigners argued there is significant overlap between recreational and medicinal use, and that the current New Zealand medicinal regime is too strict to facilitate all forms of cannabis use for medical and well being. In addition, implementation of the New Zealand Medicinal Cannabis Scheme has been slow with no products approved under the scheme to date . Kilmer and MacCoun  have argued that in the U.S. the legalisation of medicinal cannabis facilitated the subsequent passage of recreational law reform in a number of ways, but it takes time and exposure to the new legal medical market before public perceptions and other forces improve conditions for recreational law reform. Another strong predictor of supporting the CLCB was the intention to vote for the Green political party. This is understandable given the central role the Green Party played in negotiating for the referendum to be held, and their long history of advocacy for cannabis law reform in New Zealand, including the pioneering Rastafarian Green MP Nandor Tanczos, and prominent role of Green MP Chloe Swarbrick in the pro-referendum campaign for the CLCB. As outlined earlier, support for cannabis legalisation in the U.S. has also been found to be consistently higher amongst left and centre left voters . The strong support for the CLCB amongst those who live in small towns is more difficult to interpret. Large-scale outdoor illegal cannabis cultivation has been common in some rural regions of New Zealand for decades, and this activity has been associated with gang activity, arson, property vandalism and exclusion zones where residents are afraid to visit for fear of growers and improvised security devices . Those living in small towns may view legalisation as a means to resolve these problems through permitting legal regulated cannabis cultivation. Illegal cannabis cultivation has also been identified as a critical source of seasonal income in some economically depressed rural regions in New Zealand, generating hundreds of millions of dollars per year , and legalisation may be viewed as a means to transition this illegal activity to legitimate economic development.

Studies in Brassica oleracea showed the same asymmetrical interploidy compatibility pattern as we observed in C. sativa; that is, when the paternal parent had the higher chromosome number, there was a lethal disruption in embryo development, whereas when the maternal parent contained a chromosome excess, viable seeds were formed . Imbalances in the expression levels of the AGAMOUS-like gene families appeared to play important roles in the endosperm and embryo development failure in B. oleracea . Research on potato showed that the strength of triploid block can vary among genotypes . Therefore, research into multiple genotypes and gene expression variations may be useful in obtaining a full understanding of asymmetrical compatibility and asymmetric triploid blocking in C. sativa as a species. Plant growth, development, metabolism, and morphology can be greatly manipulated by the quality and duration of light . Light quality denotes the color or wavelength adjacent to the surface of the plant, which affects plant growth, foliar and floral morphology, biochemical changes, and photosynthesis process . It was demonstrated that wavelengths ranging from 430 to 500 nm is effective for pigmentation, secondary metabolites production, chloroplast development, and functioning in photosynthesis . The wavelength range 500–600 nm also influences chlorophyll production and photosynthetic activity . On the other hand, the wavelength range 640–670 nm was found effective in leaf area, photosynthetic activity, and plant biomass accumulation . Light quality and quantity also have a drastic effect on the excitation of PS I and PS II, which is directly interlinked with photosynthesis processes . Light spectral quality considerably affects plant shoots and roots regarding their growth and morphology, and their interaction .

In the present experiment, the longest RL was recorded from L1 and L9, and the opposite result was found from L2 and L6 . In a previous study, plant height and weight were found better in red light; RL was longer in red and natural light while shorter in white and blue light under greenhouse conditions . In the present study, the addition of FR light to R and B increased the LL and LW, best trimming trays while decreasing the LN and NN . It was reported that the cannabis plant attained a higher plant height and leaf area in white light compared to the combination of red and blue light , but we did not find any significant differences in those morphological traits under similar light conditions. In a previous study, the addition of FR to R and B decreased the LL and SL of tomato plants while no significant effect was observed for RL and LN . The PCA analysis revealed that LL, LW, and SL were negatively correlated with LN and NN . Results indicated that a higher number of leaves and branches will make the hemp plants shorter in size with narrow leaves and vice versa. Importantly, LN and NN were closely associated with the treatments L9, L10, and L11, whereas LL and LW manifested an opposite relationship with them . This may be due to the influence of UV-A, which reduced the leaf area but increased the leaf number and branching. Generally, UV radiation impacts the phytohormone auxin levels higher in leaf regions with high division activity and lower in areas of cell expansion , resulting in a decrease in adaxial pavement cell expansion . Furthermore, compared to white light, PFW, PGR, and NN increased in most LED composition. The results indicate the incapability of monochromatic white light for plant growth and development, as it also resulted in lower TSC and sucrose accumulation in most cases. The PCA analysis indicated a negative relationship between the L2 treatment and NN, PFW, PGR, TSC, and sucrose, which also had a positive correlation with the parameters. An earlier study showed that the Chl a and Chl b contents increased in lettuce, basil, spinach, kale, and pepper under different combinations of R and B . In our study, the Chl a and b of hemp plants were significantly increased, but the chlorophyll a/b ratio and Car drastically decreased in the L3 treatment compared to L1 . Besides this, Chl a and b significantly increased, and the Chl a/b ratio significantly decreased in all treatments, while the carotenoid concentration was found decreased in the L2, L3, L4, L6, and L9 treatments compared to L1 . Similar results from a previous study described that a high ratio of both R:B and R:B:W manifested higher chlorophyll compared to natural light in Silene capitate Kom. . Each of the plant pigments has been characterized by an absorbance pattern in wavelength called the absorbance spectrum, where the blue and red regions are absorbed strongly by Chl a and b, with less absorbance of other wavelengths . It is also known that the Chl and Car pigments absorb 400– 500 nm and 630–680 nm in the light spectrum in plants with the help of light-harvesting antenna .

The positive influence of red and blue light on Chl synthesis in the present study complies with these findings . Furthermore, the accumulation of Car and the Chl a/b ratio were increased, whereas Chl b was decreased significantly under the spectra composed with green light when compared to the red and blue spectra . Since red and blue light are absorbed by photosynthetic pigments more strongly, their influence is predominant in the upper cell layers, while green light can penetrate deeper into leaf tissues and excite the photosystem in the deeper cell layer . On the other hand, Car are lipid-soluble colored pigments that mostly consist of carotenes and xanthophylls , whose absorbance range extend into the green region , effectively cover the poorest region of chlorophyll absorbance . Thus, the addition of green light along with others in the present study might increase the concentration of Car. The photochemical activity of photosystem II is expressed by Fv/Fm, which characterizes the maximum efficiency of the photochemical activity under PS II , where Fv , Fm, and F0 denotes the maximal variable fluorescence, maximal fluorescence intensity, and fluorescence intensity at 50 µs, respectively. The photosynthetic fluorescence is a byproduct of the photosynthetic process created by trapping light energy at the reaction center within a photosynthetic membrane and after being used in photochemistry that dissipates along with heat energy . A decreasing trend in Fv/Fm was observed in the treatments L1, L6, L7, and L10 in the present study . A lower Fv/Fm may be a consequence of decreasing Fm, since F0 does not change too much in light stress .Proline is an important compound as its synthesis and catabolism play an important role in the stress adaptation of plants by keeping in balance the redox reaction . Under stress conditions, ROS-mediated regulation, including H2O2, can upregulate P5CS and downregulate PRODH activity in the plant, which can trigger the biosynthesis of proline . Over biosynthesis of proline by the over expression of P5CS may play an important role in flower initiation and bolting promotion at the early stage of plant development . Lower photosynthetic pigments and fluorescence with higher accumulation of proline in the present study indicate a stress response of plants in the L1 treatment . This stress may be due to the lower intensity of natural light under greenhouse conditions. Carbohydrates are the main source of energy and are considered the main criterion of cell division activity in plants, and their concentration depends on the amount of photosynthetically active radiation . In a previous study, it was reported that UV-A light influenced the plants to accumulate more carbohydrates , whereas at a low R:FR ratio plants accumulated more soluble sugar, carbohydrates, and secondary metabolites . The ratio of red spectrum ranged from 40 to 60%, with other light sources increasing the TSC and sugar in L7, L8, L9, and L10 . The monochromatic red, blue, and their combined spectra manifested decreased soluble carbohydrate in Anthurium cut flowers in a previous study . Our present study also found a lower TSC and sucrose content in combined red-blue spectra compared to all other treatments.

From the PCA analysis, it can be revealed that both the TSC and sucrose content manifested a negative correlation with SL, LL, and LW and are closely associated with the L9 treatment. A possible explanation is based on the fact that under stress plants produce excess carbon skeletons to prevent the declining trend in photosynthetic rate and growth in plants, which help to increase osmolytes production . The reduced photosynthetic pigments , LL, and LW under the L9 treatment in the present study quite support this hypothesis. Our study found a similar pattern of TSC and sucrose content while little dissimilarities were also observed from ascorbic acid under different light spectra. It was narrated that TSC are the precursor for ascorbic acid biosynthesis, and mature green tomatoes can achieve both compounds in higher amounts under high irradiance of light, but no correlations were observed in a series of experiments between them . These results indicate that the accumulation of sucrose content and TSC is interdependent, whereas ascorbic acid is independent of both compounds. Moreover, plants accumulate all osmoprotectant molecules significantly higher when the green light was added to the other light spectra , compared to the red and blue combination . Since ancient times, wild or naturalized plants have provided social security to millions of people globally, in the form of fuel, food, fodder, supplements, raw materials for industries, medicines, and especially a source of additional income . According to the World Health Organization, about 65–80% of people in developing countries are reliant on herbal remedies made from medicinal plants . About 90% of the plant species used in the Indian herbal industry come from the Western Himalayas . The Indian Himalayan region was well-known for its floristic diversity, with approximately 1748 medicinal plant species reported from the region , which were used in various fields of chemistry, pharmacological research, pharmacognosy, and clinical therapeutic studies . Himachal Pradesh is the northeastern state of India, geographically divided into three distinct regions; the outer Himalayas , the mid-hills, and the greater Himalayas, which cover an area of 55,673 km2 . Due to its diverse climatic, topographic, and geographical position or altitude, the state of Himachal Pradesh represents a rich source of biodiversity . According to the data of the Ayurvedic Pharmacopoeia Committee , out of 1100 single-ingredient drugs, 350 plant species belong to native therapeutic groups, among which 225 species blooms in the state of Himachal Pradesh and were obtained commercially . Angiosperms, including 1003 species of dicotyledons, belonging to 498 genera and 313 species of monocotyledons, belonging to 133 genera. Whereas, the gymnosperms are characterized by only 10 species and 8 genera in the state . The contribution of dicotyledons and monocotyledons to the world flora is approximately 81.3 and 18.7 percent, respectively, trimming tray with the Shimla district accounting for 23.3 percent of monocotyledon species . Approximately 500 species of medicinal plants have been reported from Himachal Pradesh .

From the very beginning of human civilization, people have been developing their knowledge of plant use, management, and conservation . Indigenous people seem to have a hierarchical knowledge of these traditional medicinal plants for a variety of human diseases, and this knowledge has been passed on from one generation to the next . This study documents the accumulated knowledge regarding plants in the Maraog region that has traditionally been employed for the treatment of different human diseases. No such study has been conducted previously in this area, thus it will assist in providing valuable information to the ethnomedicinal research field, and such information is expected to be useful in the discovery of drugs . Such studies have been done indifferent parts of the world, including Pakistan, Nepal, Africa, America, Europe, Poland, Argentina, Australia, Iran, New Zealand, Turkey, Japan, Taiwan, Pakistan, China, Nepal, as well as different parts of South, North and East India. The declining rate of ethnomedicinal knowledge amongst younger generations was found to be a common problem in all the reported countries . As the economic condition of people living in rural areas is improving day-by-day, people are becoming less dependent on traditional medicinal practices, thus knowledge in the use of medicinal plants is also diminishing .

In this case series, we present 2 cases of MC in male adolescents following recreational vaporized cannabis use.Patient A00 is a 15-year-old boy with a past psychiatric history significant for nonsuicidal self-injurious behavior via cutting, history of childhood trauma, no prior suicide attempts or inpatient hospitalizations, and no known past medical history. He presented to the emergency department  with 5 days of aggressive behavior, paranoia, auditory hallucinations, and hyperreligiosity. He endorsed a history of vaping “TKO” marijuana most days of the week for approximately 1 year before presentation and no other substance use. In our ED, his vital signs were notable for tachycardia to 114 beats per minute, temperature of 37.6 Celsius, and hypertension to 171/111 mmHg. Workup in the ED revealed a leukocytosis to 11.2 K/UL, hemoglobin of 15.0 G/DL, hematocrit of 45%, and serum creatine kinase of 408 U/L. Urine drug screen was positive only for cannabis.He experienced episodes of emesis in the ED. Physical examination was notable for mydriasis, psychomotor retardation, and hyperreflexia. His mental status examination was significant for poor eye contact, monotone speech, flat affect, and disorganized thought process. After 2 doses of lorazepam 2mg by mouth and hydralazine 10mg PO, his blood pressure improved to 142/97 mmHg. He was admitted to the general pediatrics service for further workup and management of persistent hypertension and tachycardia. On arrival to the floor, he had a heart rate of 124 beats per minute and a blood pressure of 136/84 mmHg. Urine metanephrines, plasma renin and aldosterone, magnetic resonance image brain without contrast,hydroponic grow tent cerebrospinal fluid studies were all within normal limits. Continuous electroencephalography revealed diffuse low-voltage fast activity but no epileptiform discharges or generalized slowing. Due to ongoing autonomic instability, on hospital day 1, treatment with lorazepam 2mg three times daily as needed for hypertension was started, and he received 4 mg total over 24 hours. On hospital day 2, he reported feeling stiff in his arms and legs and “feeling stuck in his body” and was noted to appear withdrawn with minimal speech output.

The pediatric consultation-liaison psychiatry service was consulted for concern of altered mental status and recent bizarre behavior. On the initial examination by the pediatric consultation-liaison psychiatry service, he was noted to be paranoid with a tangential thought process and significant psychomotor retardation. The initial Bush-Francis Catatonia Rating Scale was 7. He had received lorazepam 2 mg PO x2 the day prior. On serial examinations, he had catalepsy, waxy flexibility, and defificits with attention and calculation. Lorazepam was scheduled 2 mg PO t.i.d. Over the 18-day admission, lorazepam was titrated to 12 mg daily. Psychotic symptoms resolved, though attention deficits persisted. He was discharged to an inpatient psychiatric unit with treatment with lorazepam 11mg per day. He was hospitalized there for 5 days and then discharged on 9 mg daily with instructions to taper over the next 18 days. He re-presented to the ED with catatonia and suicidality 3 weeks later in the context of repeat vaporized cannabis use. He presented with depressed affect but no psychosis.He was transferred to an inpatient psychiatric facility. After discharge, he tapered off of benzodiazepines over 3 months and has remained without symptoms.“Patient B” is a 16-year-old boy with a past psychiatric history significant for attention-deficit/hyperactivity disorder, who was brought to the ED for altered mental status after vaping cannabis. He noted a history of smoking cannabis but reported vaping cannabis the day before ED presentation. Of note, he had been admitted to an outside hospital several months prior for a similar episode of catatonia after reported cannabis use. As per documentation from that hospitalization, catatonic symptoms resolved with lorazepam treatment. On arrival to our ED, he was afebrile but hypertensive to 138/70 mmHg and tachycardiac to 100 beats per minute. Blood work was significant for hemoglobin of 14.8 g/dl , hematocrit of 46.1% , thrombocytosis to 407 K/UL, creatine kinase of 759 U/L, and urine drug screen was positive only for cannabinoids.On physical examination, he was slow to respond to questions and had difficulty following simple commands. He was described as “dazed” and appeared to be responding to internal stimuli; he was too behaviorally dys regulated to meaningfully participate in medical workup or safety assessment, so he was given haloperidol 5 mg IM and lorazepam 2 mg IV, before psychiatric consultation. Four hours after the administration of these medications, he developed writhing motions of his head and neck, thought to be an adverse reaction to haloperidol, which resolved with the administration of diphenhydramine 50 mg PO. Several hours later, he developed rigidity and psychiatry was consulted owing to concern for catatonia. On initial psychiatric evaluation , he scored 8 on the initial Bush-Francis Catatonia Rating Scale .

In light of these findings, a diagnosis of MC was made and treatment with lorazepam 2 mg PO/IV every 6 hours was recommended. He received a total of 6 mg of lorazepam IV in the ED with resolution of his rigidity. Owing to worsening hypertension to 158/68 mmHg, dysregulated behavior, and development of a 2-liter oxygen requirement after lorazepam administration, he was admitted to a medical intensive care unit for continued monitoring and treatment of MC. In the medical intensive care unit, further workup revealed new hyperkalemia to .5.8 mmol/L and uptrending creatine kinase level to 1800 U/L, which were treated with intravenous fluids. Computed tomography of his head without contrast was negative for acute abnormalities. He received 1 additional dose of lorazepam 2 mg IV in the medical intensive care unit , and his rigidity, mutism, staring, hallucinations, and oxygen requirement subsequently resolved. He was transferred to the general pediatrics floor where he was noted to have perseverative speech, intermittent aggression toward staff, and deficits on bedside cognitive testing including poor short-term recall and poor attention. Cardiology was asked to see him to comment on his intermittent hypertension and electrocardiogram changes; a repeat electrocardiogram did not show left ventricular hypertrophy, and an echocardiogram was unremarkable. On hospital day 2, his initial Bush Francis Catatonia Rating Scale was 0 on evaluation by the pediatric consultation-liaison psychiatry service, and scheduled lorazepam was decreased to 2 mg PO t.i.d. On this dose of lorazepam, he remained normotensive and without cognitive deficits or signs of catatonia or psychosis on exam. He was ultimately discharged on hospital day 5 to outpatient psychiatric care.Case reports of substance-induced catatonia in this age group have included catatonia secondary to ecstasy and synthetic cannabis.To the best of our knowledge, the two cases described here represent novel reports of presentations of pediatric MC in the setting of vaporized cannabis use. These cases raise the question if vaporized cannabis use has the potential to be a causative factor in the development of catatonia. Vaping devices facilitate the use of cannabis concentrates, which have been found to have approximately triple the delta-9- tetrahydrocannabinol strength of flower-derived strains.Vaporized cannabis use has been associated with both increased plasma levels of delta-9- tetrahydrocannabinol and subjective drug effects compared with cannabis use via smoking.Highpotency delta-9-tetrahydrocannabinol has been associated with increased negative psychiatric effects such as low mood and anxiety,suggesting the potential for other neuropsychiatric sequelae as well. In these 2 cases, while the completed workup was unrevealing for acute neurologic, infectious, or metabolic precipitants to catatonia, we were limited in our ability to test for all drugs of abuse.

Synthetic cannabinoid and cathinone testing were sent out tests at our institution, and these tests were deferred owing to cost and low likelihood to change management. We considered psychiatric decompensation as the acute precipitants to catatonia in both of these patients. Neither patients endorsed acute emotional distress before presentation, but patient A reported feeling depressed in the setting of ongoing psychosocial stress suggesting the possibility of an affective component as well in this case. It is also unclear from documented history if either patient had a loss of functioning consistent with a prodrome of a primary psychotic disorder before presentation. The acute onset of psychotic symptoms and timeline in relation to cannabis use more strongly suggests psychotic symptoms in both cases were substance-induced, but we cannot exclude the possibility of an underlying vulnerability to a primary psychotic disorder in either patient. In either patient, vaporized cannabis may have lowered the threshold to the development of catatonia given its effects on the gammaaminobutyric acid  system. The autonomic instability in the context of catatonic symptoms led us to define these 2 presentations as malignant catatonia. Although the neurobiological underpinnings of catatonia are not well understood,there is evidence supporting alterations in GABA, dopamine, and glutamate in the pathogenesis of this disorder.Clinically, involvement of the GABAergic system in catatonia is suggested by the rapid and often dramatic efficacy of GABA agonists, such benzodiazepines, for the treatment of the syndrome.Exposure to cannabinoid receptor 1 agonists,cheap grow tents such as delta-9-tetrahydrocannabinol, has been associated with disruption of GABAergic-mediated cortical inhibition.Given the importance of cortical GABAergic modulation of feedback loops within mesostriatal and mesocorticolimbic systems,further research is needed to investigate if disturbance in GABA by delta-9-tetrahydrocannabinol may directly precipitate many of the psychomotor symptoms seen in catatonia.Amid the pandemic caused by the novel coronavirus disease , public health measures were enacted in countries around the world to curb the spread of COVID-19. In Canada, wide-scale emergency measures were put in place in March 2020 that severely impacted Canadians’ ability to engage in work, educational, recreational, and social activities. During times of high stress and anxiety, social isolation, and limited out-of-home recreational activities such as those seen during the COVID-19 pandemic, people may increase their use of substances like cannabis . Cannabis is the most widely used psychoactive substance besides alcohol in Canada, and its use can be accompanied by the risk of developing a cannabis use disorder along with numerous short-term and long-term adverse health consequences . Alongside the implementation of COVID-19-related emergency measures, a Statistics Canada survey reported a sharp increase in cannabis sales in March and April 2020 compared with previous months .

Further, a survey of Canadian adults found that among cannabis users, approximately half increased their use of cannabis relative to their pre-pandemic consumption patterns . The widespread use of cannabis and an increase in use during the current COVID-19 pandemic underscores the necessity of understanding the etiology of elevated levels of cannabis use. A key determinant of a substance’s use and misuse is its reinforcing value, which refers to its behavior-strengthening and behaviormaintaining properties . The reinforcing value of a substance has been operationalized as behavioral economic demand, or the relationship between the price of a substance and its consumption. Substance-related demand has been measured in the lab through the use of hypothetical purchase tasks . Purchase tasks have been employed across a number of substances including alcohol, tobacco, and cocaine , and more recently for cannabis . These tasks ask the participant to estimate their consumption of a substance at varying price points . Purchase tasks allow for the characterization of an individual’s pattern of demand via the calculation of several demand indices: four observed indices  and one derived index . Intensity refers to unconstrained consumption at zero cost. Omax refers to the peak expenditure, or the maximum total amount of money spent on the substance across price points. Pmax is the price at which this peak expenditure occurs. Breakpoint refers to the cost at which consumption is suppressed to zero. Higher values on each of these indices reflect higher demand for the substance. The derived index, elasticity, refers to the rate at which consumption decreases relative to increases in cost. Latent factor analysis of the Marijuana Purchase Task has revealed that these five indices map onto two underlying dimensions of demand. The first factor is “Amplitude,” which refers to consumption at unrestricted cost and is comprised of one index, intensity. Higher consumption at zero cost reflects higher demand. The second factor, “Persistence,” is comprised of Omax, Pmax, breakpoint, and elasticity, and reflects the individual’s sensitivity to increasing cost . A low sensitivity to increasing cost indicates higher demand. This factor structure aligns with research demonstrating a similar structure for alcohol and tobacco purchase tasks .