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Sex differences in the acute effects of smoked cannabis: evidence from a human laboratory study of young adults

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Rationale Animal studies have found robust sex differences in the pharmacokinetics and pharmacodynamics of Δ⁹-tetrahydrocannabinol (THC). However, the human evidence remains equivocal, despite findings that women may experience more severe consequences of cannabis use than men. Objectives The objective of this secondary analysis was to examine sex differences in THC pharmacokinetics and in acute subjective, physiological, and cognitive effects of smoked cannabis in a sample of regular cannabis users (use 1–4 days per week) aged 19–25 years. Methods Ninety-one healthy young adults were randomized to receive active (12.5% THC; 17 females, 43 males) or placebo (< 0.1% THC; 9 females, 21 males) cannabis using a 2:1 allocation ratio. Blood samples to quantify concentrations of THC, 11-OH-THC, and 11-Nor-carboxy-THC (THC-COOH), as well as measures of subjective drug effects, vital signs, and cognition were collected over a period of 6 h following ad libitum smoking of a 750-mg cannabis cigarette. Results Females smoked less of the cannabis cigarette than males (p = 0.008) and had a lower peak concentration of THC and THC-COOH than males (p ≤ 0.01). Blood THC concentrations remained lower in females even when adjusting for differences in estimated dose of THC inhaled. There was very little evidence of sex differences in visual analog scale (VAS) ratings of subjective drug effects, mood, heart rate, blood pressure, or cognitive effects of cannabis. Conclusions Females experienced the same acute effects of smoked cannabis as males at a lower observed dose, highlighting the need for more research on sex differences in the pharmacology of THC, especially when administered by routes in which titrating to the desired effect is more difficult (e.g., cannabis edibles).
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Sex differences in the acute effects of smoked cannabis: evidence
from a human laboratory study of young adults
Justin Matheson
&Beth Sproule
&Patricia Di Ciano
&Andrew Fares
&Bernard Le Foll
Robert E. Mann
&Bruna Brands
Received: 26 April 2019 /Accepted: 22 September 2019
#Springer-Verlag GmbH Germany, part of Springer Nature 2019
Rationale Animal studies have found robust sex differences in the pharmacokinetics and pharmacodynamics of Δ
cannabinol (THC). However, the human evidence remains equivocal, despite findings that women may experience more severe
consequences of cannabis use than men.
Objectives The objective of this secondary analysis was to examine sex differences in THC pharmacokinetics and in acute
subjective, physiological, and cognitive effects of smoked cannabis in a sample of regular cannabis users (use 14 days per week)
aged 1925 years.
Methods Ninety-one healthy young adults were randomized to receive active (12.5% THC; 17 females, 43 males) or placebo (<
0.1% THC; 9 females, 21 males) cannabis using a 2:1 allocation ratio. Blood samples to quantify concentrations of THC, 11-OH-
THC, and 11-Nor-carboxy-THC (THC-COOH), as well as measures of subjective drug effects, vital signs, and cognition were
collected over a period of 6 h following ad libitum smoking of a 750-mg cannabis cigarette.
Results Females smoked less of the cannabis cigarette than males (p= 0.008) and had a lower peak concentration of THC and
THC-COOH than males (p0.01). Blood THC concentrations remained lower in females even when adjusting for differences in
estimated dose of THC inhaled. There was very little evidence of sex differences in visual analog scale (VAS) ratings of
subjective drug effects, mood, heart rate, blood pressure, or cognitive effects of cannabis.
Conclusions Females experienced the same acute effects of smoked cannabis as males at a lower observed dose, highlighting the
need for more research on sex differences in the pharmacology of THC, especially when administered by routes in which titrating
to the desired effect is more difficult (e.g., cannabis edibles).
Keywords Sex differences .THC .Cannabis .You n g adult s
Electronic supplementary material The online version of this article
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material, which is available to authorized users.
*Justin Matheson
Department of Pharmacology and Toxicology, Faculty of Medicine,
University of Toronto, 27 Kings College Circle,
Toronto, Ontario M5S 3H7, Canada
Institutefor Mental Health Policy Research, Centre for Addiction and
Mental Health, 33 Russell Street, Toronto, Ontario M5S 2S1, Canada
Leslie Dan Faculty of Pharmacy, University of Toronto, 144 College
Street, Toronto, Ontario M5S 3M2, Canada
Pharmacy Department, Centre for Addiction and Mental Health,
1001 Queen Street, Toronto, Ontario M6J 1H4, Canada
Department of Psychiatry, Faculty of Medicine, University of
Toronto, 250 College Street, Toronto, Ontario M5T 1R8, Canada
Translational Addiction Research Laboratory, Centre for Addiction
and Mental Health, 33 Russell Street, Toronto, Ontario M5S 2S1,
Campbell Family Mental Health Research Institute, Centre for
Addiction and Mental Health, 250 College Street,
Toronto, Ontario M5T 1R8, Canada
Department of Family and Community Medicine, Faculty of
Medicine, University of Toronto, 500 University Avenue, 5th Floor,
Toronto, Ontario M5G 1V7, Canada
Dalla Lana School of Public Health, University of Toronto, 155
College Street, Toronto, Ontario M5T 3M7, Canada
Controlled Substances Directorate, Health Canada, Ottawa, Ontario,
Psychopharmacology (2020) 237:305316
/Published online: 22 October 2019
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
... The effects of THC on mood have not been consistent in previous studies. Some studies showed no effect of THC on mood (73)(74)(75), while others demonstrated negative effects (76)(77)(78), whereas a more recent study showed elevated scores on positive states (79,80). These inconsistencies in the effect of THC on mood can possibly be explained by essential differences in study designs, such as differences in dose, route of administration, time of assessment after dosing, and participants' drug use history. ...
... With regard to sexes, there have been suggestions that women are more sensitive to the effects of THC than men (82). However, several studies were unable to confirm this, showing no differences between men and women in the acute effect of THC on neurocognitive function (80,83). In the current study, it is also unlikely that sex differences significantly affected the study results. ...
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Due to differences in potency, efficacy, and affinity for CB1 receptors, similarities and differences in psychoactive effect profiles of natural cannabis and synthetic cannabinoids (SCs) cannot reliably be derived from equipotent dose comparisons. Instead, the current study proposes to compare the intrinsic psychoactive effects of natural cannabis (THC) and an SC, JWH-018, at psychotropic dose equivalence. Participants from two placebo-controlled studies were matched for their levels of subjective high to compare neurocognitive and psychotomimetic effects of THC and JWH-018. At equal subjective intoxication levels, both drugs impaired psychomotor, divided attention, and impulse control, with no significant difference between the two drugs. Both drugs also caused significant psychotomimetic effects, but dissociative effects were considerably more pronounced for JWH-018 than THC. We conclude that psychotropic dose equivalence provides a uniform approach for comparing the neurocognitive and psychotomimetic profiles of CB1 agonists, which can also be applied to other drug classes.
... Cannabis use and cannabis use disorder have a more significant effect on selfreported mental health quality of life among women than men (96). Human laboratory research has suggested that females experience the same subjective effects as males after smoking less cannabis, which recapitulates some of the sex differences in acute cannabinoid effects observed in animal models (97,98). Human research has shown that gender significantly impacts access to cannabis and patterns of cannabis use, with men/boys significantly more likely to use cannabis than women/girls (99). ...
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Cannabis legalization for non-medical purposes (subsequently referred to as “cannabis legalization” or “legalization”) took place in Canada in October 2018. One of the federal government's stated goals with cannabis legalization was to protect Canadian youth from cannabis-related harms. The main objective of this narrative review is to describe the impact of cannabis legalization on Canadian youth. To that end, we discuss the regulation of the Canadian cannabis market, outline changes in the epidemiology and parameters of cannabis use (modes of use, potency of cannabis) among youth, and discuss prevention and education initiatives related to cannabis. The Canadian model differs from other jurisdictions that legalized recreational cannabis use, especially with regard to a higher degree of government regulation of the cannabis market. Another difference is the development and endorsement of lower-risk cannabis use guidelines to educate the public and health professionals. The results available for this review cover only 3 years post-legalization. Cannabis legalization in Canada brought an apparent increase in use among Canadian older than 25. However, results for youth are mixed, with the majority of studies showing no pronounced increase. Notably, the trend of a decrease in adolescents' cannabis use seen pre-legalization may have reversed. Emerging evidence also suggests that cannabis-related hospitalizations and emergency department visits among Canadian youth may have increased due to cannabis legalization. Data about changes in the age of initiation, the influence of legalization on sex and gender, and race/ethnicity are limited, with evidence suggesting that the age of initiation slightly increased. So far, there is limited data about the impact of cannabis legalization on Canadian youth. Further long-term monitoring and research to assess the effects of cannabis legalization on Canadian youth.
... Whereas initial studies did not report any differences in the acute subjective effects of cannabinoids (Cocchetto et al. 1981), or reported more pronounced rewarding effects in men (Haney 2007;Penetar et al. 2005), most recent findings are aligned with the previously mentioned preclinical data and have revealed an increased sensitivity to the subjective (Makela et al. 2006;Fogel et al. 2017;Haney 2009, 2014;Mathew et al. 2003) effects of cannabis in women, especially in low doses (Fogel et al. 2017). In a 2020 study of the acute effects of smoked cannabis in men and women, in which participants were permitted to smoke cannabis ad libitum in order to titrate to their desired intoxication, Matheson and colleagues reported similar effects in men and women, despite the women demonstrating significantly lower quantities of cannabis consumed and significantly lower levels of blood THC and THC metabolites (Matheson et al. 2020). This suggests that women demonstrated acute effects of cannabis equal to those reported by men at a significantly lower dose. ...
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Background Cannabis is the most common illicit drug used in the USA and its use has been rising over the past decade, while the historical gap in rates of use between men and women has been decreasing. Sex differences in the effects of cannabinoids have been reported in animal models, but human studies are sparse and inconsistent. We investigated the sex differences in the acute subjective, psychotomimetic, cognitive, and physiological effects of intravenous (IV) delta-9 tetrahydrocannabinol (THC), the main psychoactive constituent of cannabis. Methods Healthy male and female individuals, with limited exposure to cannabis, participated in a double blind, placebo-controlled study of intravenous (IV) placebo or THC at two doses (0.015 mg/kg and 0.03 mg/kg). Visual analog scale (VAS) was used to measure subjective effects, Psychotomimetic States Inventory (PSI) and the Clinician-Administered Dissociative Symptoms Scale (CADSS) were used to assess the psychotomimetic effects and perceptual alterations, respectively, and Rey Auditory Verbal Learning Task (RAVLT) was used to evaluate cognitive effects. Outcome variables were represented as the peak change from baseline for each variable, except RAVLT which was used only once per the test day after the subjective effects. Results A total of 42 individuals participated in this study. There were no significant differences between male and female participants in background characteristics. There was a significant main effect of sex on the VAS scores for THC-induced “High” (F1,38 = 4.27, p < 0.05) and a significant dose × sex interaction (F2,77 = 3.38, p < 0.05) with female participants having greater “High” scores than male participants at the lower THC dose (0.015 mg/kg). No other sex differences were observed in acute subjective, psychotomimetic, cognitive, or physiological effects of THC. Conclusion There were significant sex differences in subjective effects of feeling “High” at a lower dose of THC. However, there were no other sex-related differences in the subjective, physiological, or cognitive effects of THC.
Executive functions including working memory (WM) and attention are altered following Cannabis exposure in humans. To test for similar effects in a rodent model, we exposed adult male rats to acute Cannabis smoke before testing them on touchscreen-based tasks that assess these executive processes. The trial-unique, delayed nonmatching-to-location (TUNL) task was used to evaluate WM, task performance at different spatial pattern separations, and response latencies. The five-choice serial reaction time task (5-CSRTT) was used to measure attention, impulsivity, perseveration, and response latencies. Rats were exposed acutely to high- Δ⁹-tetrahydrocannabinol (THC), low-CBD (Mohawk) and low-THC, high-CBD (Treasure Island) strains of Cannabis smoke using a chamber inhalation system. The effects of Cannabis smoke were directly compared to systemic Δ⁹-THC injection (3 mg/kg; i.p.). TUNL task performance was significantly impaired following acute high-THC smoke exposure or THC injections, but not low-THC smoke exposure, with no effects on response latencies. Fewer total trials and selection trials were also performed following THC injections. Performance was poorer for smaller separation distances in all groups. Neither acute smoke exposure, nor injected THC, impacted attentional processes, impulsivity, perseverations, or response latencies in the 5-CSRTT. Pharmacokinetic analysis of rat plasma revealed significantly higher THC levels following injections than smoke exposure 30 minutes following treatment. Exposure to low-THC, high-CBD Cannabis smoke significantly increased CBD in plasma, relative to the other treatments. Taken together, our results suggest that WM processes as measured by the TUNL task are more sensitive to THC exposure than the attentional and impulsivity measures assessed using the 5-CSRTT.
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Rationale Researchers have traditionally studied the effects of psychoactive drugs such as Cannabis in controlled laboratory settings or relied on retrospective self-reports to measure impairment. However, advances in technology afford opportunities to conduct assessments remotely. Objectives We considered whether objective click-stream data (time and number of clicks spent on a webpage) during an online survey could supplement self-reports of substance use problems. Methods The clickstream data of participants (n = 236) were examined as they completed an online study which included validated psychometric tests (Cannabis Use Disorders Identification Test-Revised, Grit-O, Kessler Psychological Distress Scale, and Brief Self Control Scale). Clickstream data were compared to self-reported Cannabis use. Results People reporting Cannabis use within the last 4 weeks required more time and more clicks to complete the online survey, and this was specifically associated with reported frequency of use, duration of impairment, and problems with memory and concentration. Longer amounts of time and more clicks on the online questionnaire were associated with more recent Cannabis use rather than demographic factors or stimulant use. Conclusions These results imply clickstream data remotely detected indecision or other deficits associated with previous Cannabis use.
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Importance. While cannabis use in women is increasing worldwide, research into gender differences in cannabis use disorder (CUD) symptomology is lacking. Objective. In response to limited effectiveness of addiction treatment, research focus has been shifting from clinical diagnoses towards interactions between symptoms, as patterns of symptoms and their interactions could be crucial in understanding etiological mechanisms in addiction. The aim of the current study was to evaluate the CUD symptom network and assess whether there are gender differences therein. Design. Cross-sectional. Setting. Online self-report study. Participants. A convenience sample of 1257 weekly cannabis users, including 745 men and 512 women. Main outcome and measure. Participants completed questionnaires assessing DSM-5 CUD symptoms and additional items on plans to quit or reduce use, cigarette use, and the presence of psychological diagnoses. Gender differences were assessed for all variables and an Ising model estimation method was used to estimate CUD symptom networks in men and women using network comparison tests to assess differences. Results. The estimated networks were dense with all symptoms except for tolerance and risky use being highly central to the network. There were gender differences in the prevalence of 6 of the 11 symptoms, but symptom networks did not differ between men and women. Cigarette use appeared to only be connected to the network through withdrawal, indicating a potential role of cigarette smoking in enhancing cannabis withdrawal symptoms. Furthermore, there were gender differences in the network associations of mood and anxiety disorders with CUD symptoms. Conclusion and relevance. While men and women differ in symptom prevalence, the pattern and weights of the associations between symptoms were found to be very similar. However, gender differences in the role of comorbidities in the network and the relation between smoking and withdrawal highlight the importance of gender differences in understanding CUD, which may have implications for treatment.
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Objective To provide health care providers with the best evidence on cannabis use with respect to women’s health. Areas of focus include general patterns of cannabis use as well as safety of use; care for women who use cannabis; stigma; screening, brief intervention, and referral to treatment; impact on hormonal regulation; reproductive health, including contraception and fertility; sexual function; effects on perimenopausal and menopausal symptoms; and use in chronic pelvic pain syndromes. Target Population The target population includes all women currently using or contemplating using cannabis. Outcomes Open, evidence-informed dialogue about cannabis use, which will lead to improvement in patient care. Benefits, Harms, and Costs Exploring cannabis use through a trauma-informed approach provides the health care provider and patient with an opportunity to build a strong, collaborative, therapeutic alliance. This alliance empowers women to make informed choices about their own care. It also allows for the diagnosis and possible treatment of cannabis use disorders. Use should not be stigmatized, as stigma leads to poor “partnered care” (i.e., the partnership between the patient and care provider). Multiple side effects of cannabis use may be mistaken for other disorders. Currently, use of cannabis to treat women’s health issues is not covered by public funding; as a result, individual users must pay the direct cost. The indirect costs of cannabis use are unknown. Thus, health care providers and patients must understand the role of cannabis in women’s health issues, so that women can make knowledgeable decisions. Evidence PubMed, EMBASE, and grey literature were searched to identify studies of “cannabis use and effect on infertility, contraception, perimenopause and menopausal symptoms, and pelvic pain” published between January 1, 2018 and February 18, 2021. All clinical trials, observational studies, reviews (including systematic reviews and meta-analyses), guidelines, and conference consensus statements were included. Publications were screened for relevance. The search terms were developed using the Medical Subject Headings (MeSH) terms and keywords (and variants), including cannabis, cannabinoids, marijuana, dexanabinol, dronabinol, tetrahydrocannabinol; the specific terms to capture women’s health were estrogen, estradiol, medroxyprogesterone acetate, vaginal contraception, oral contraceptives, fertilization, amenorrhea, oligomenorrhea, pelvic pain, dysmenorrhea, endometriosis, interstitial cystitis, vulvodynia, and menopause. Validation Methods The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See online Appendix A (Tables A1 for definitions and A2 for interpretations of strong and weak recommendations). Intended Audience All heath care providers who care for women. SUMMARY STATEMENTS 1.Cannabis use is increasing, and women are commonly using cannabis for recreational and medical reasons (high). 2.Use of cannabis, especially products containing tetrahydrocannabinol, can induce or worsen psychosis and worsen depression (high). 3.Study results concerning the association between cannabis and anxiety are conflicting, and this association requires further evaluation (high). 4.Use of cannabis, similar to use of other intoxicating substances, may be associated with high-risk sexual activity (low). 5.There is no evidence that contraceptive methods are altered by cannabis use (low). 6.There is limited evidence that frequent cannabis use may affect female fertility (moderate), but frequent use can diminish male fertility (moderate). 7.There is no evidence for cannabis use for management of perimenopausal symptoms (very low). 8.There is no evidence that cannabis products improve chronic pelvic pain (low). RECOMMENDATIONS 1.Women should be screened for cannabis use, as they are for other substance use (strong, moderate), and further exploration of its impact should be initiated (strong, moderate). 2.Cannabis use can be screened for using appropriate screening tools (conditional, moderate) 3.A trauma-informed care approach and harm reduction should be used when inquiring about cannabis use (strong, low). 4.The fact that a woman uses cannabis should not influence her choice of contraceptive method (strong, moderate). 5.Couples should be counselled that cannabis use appears to affect male fertility and may have an impact on female fertility (conditional, moderate). 6.Sleep disturbances in the perimenopausal period should be characterized and other management modalities trialed before women consider using any cannabis product for this indication (strong, moderate). 7.Women should be counselled about the lack of evidence for using cannabis products to treat chronic pelvic pain (strong, moderate).
Objective To provide health care providers with the best evidence on cannabis use and women’s health. Areas of focus include screening, dependence, and withdrawal; communication and documentation; pregnancy (including maternal and fetal outcomes); maternal pain control; postpartum care (including second-hand smoking and parenting); and breastfeeding. Target Population The target population includes women who are planning a pregnancy, pregnant, or breastfeeding. Benefits, Harms, and Costs Discussing cannabis use with women who are planning a pregnancy, pregnant, or breastfeeding allows them to make informed choices about their cannabis use. Based on the limited evidence, cannabis use in pregnancy or while breastfeeding should be avoided, or reduced as much as possible if abstaining is not feasible, given the absence of safety and long-term follow up data on cannabis-exposed pregnancies and infants. Evidence PubMed and Cochrane Library databases were searched for articles relevant to cannabis use during pregnancy and breastfeeding published between January 1, 2018, and February 5, 2021. The search terms were developed using the MeSH terms and keywords and their variants, including cannabis, cannabinoids, cannabidiol, CBD, THC, marijuana, edible, pregnancy, pregnant, prenatal, perinatal, postnatal, breastfeed, breastfed, lactation, nursing, fetus, fetal, neonatal, newborn, and child. In terms of publication type, all clinical trials, observational studies, reviews (including systematic reviews and meta-analyses), guidelines, and conference consensus statements were included. The main inclusion criteria were pregnant and breastfeeding women as the target population, and exposure to cannabis as the intervention of interest. Validation Methods The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See online Appendix A (Tables A1 for definitions and A2 for interpretations of strong and weak recommendations). Intended Audience All health care providers who care for women of reproductive age. SUMMARY STATEMENTS 1.Screening, brief intervention, and referral for treatment can be used to identify and treat cannabis use in women during pregnancy (low). 2.The effectiveness of cannabis for treatment of nausea and vomiting in pregnancy is unclear (very low). 3.Prenatal cannabis exposure is associated with mild fetal growth restriction (low). 4.The effects of prenatal cannabis exposure on long-term outcomes through to childhood, adolescence, and adulthood have not been conclusively defined, but recent data suggest that there are persistent neurocognitive effects into adulthood (moderate). 5.Although cannabis is commonly used to treat pain, there is no evidence for its use in alleviating pain during pregnancy, intrapartum and/or postpartum periods (very low). 6.There is little data available to inform decisions about cannabis use during breastfeeding (low). 7.Given the evidence, the safest option is to avoid cannabis use during pregnancy and breastfeeding (moderate). 8.In cases where women are unable to abstain, given the apparent dose–response relationship between prenatal cannabis exposure and persistent neurocognitive effects on the fetus and/or neonate, decreasing cannabis use during pregnancy and breastfeeding can mitigate the adverse effects (moderate). RECOMMENDATIONS 1.All women should be screened for cannabis use, including during pregnancy, using a validated screening tool (strong, low). 2.Women with at-risk cannabis use or cannabis use disorder should be offered brief intervention, and, if appropriate, referral for treatment (strong, low). 3.If possible, health care providers should document cannabis use in pregnancy, both in the prenatal record and in the infant’s medical record (strong, low). 4.Cannabis should not be used during pregnancy because prenatal exposure can increase the risk of neurobehavioural abnormalities in the child (strong, moderate). 5.Health care providers should monitor women who regularly (near daily or more than twice weekly) use cannabis during pregnancy for potential intrapartum and/or postpartum withdrawal (or cannabis withdrawal syndrome) (strong, moderate). 6.Health care providers should recommend that women abstain from cannabis use during breastfeeding (strong, low).
Résumé Objectif Fournir aux fournisseurs de soins de santé les meilleures données probantes sur l’utilisation de cannabis et la santé des femmes. Les domaines d’intérêt sont : les profils généraux d’utilisation du cannabis ainsi que la sécurité de la consommation; les soins aux femmes qui utilisent le cannabis; la stigmatisation; le dépistage, l’intervention brève et l’orientation vers le traitement; les effets sur la régulation hormonale; la santé reproductive, y compris la contraception et la fertilité; la fonction sexuelle; les effets sur les symptômes périménopausiques et postménopausiques; et l’utilisation dans le traitement des syndromes de douleur pelvienne chronique. Population cible La population cible comprend toutes les femmes qui consomment ou utilisent du cannabis ou qui envisagent de le faire. Résultats Un dialogue ouvert et fondé sur des données probantes relativement à l’utilisation et la consommation de cannabis, dialogue qui mènera à l’amélioration des soins aux patientes. Bénéfices, risques et coûts L’exploration de l’utilisation et de la consommation de cannabis par une approche basée sur la connaissance des traumatismes donne l’occasion au fournisseur de soins et à la patiente de créer une solide alliance thérapeutique collaborative. Cette alliance permet aux femmes de faire des choix éclairés sur leurs propres soins. Elle facilite également le diagnostic et le traitement possible des troubles de l’usage du cannabis. Il ne faut pas stigmatiser la consommation, car la stigmatisation nuit à l’alliance thérapeutique (c’est-à-dire le partenariat entre la patiente et le fournisseur de soins). Plusieurs effets indésirables de la consommation de cannabis peuvent être confondus avec d’autres problèmes de santé. À l’heure actuelle, l’utilisation du cannabis pour traiter les problèmes de santé féminine n’est pas financée par le secteur public; par conséquent, les utilisatrices doivent assumer les coûts directs. Les coûts indirects de l’utilisation de cannabis sont inconnus. Ainsi, les fournisseurs de soins et les patientes doivent comprendre le rôle du cannabis dans les problèmes de santé féminine de sorte que les femmes puissent prendre des décisions éclairées. Données probantes Des recherches ont été effectuées dans PubMed, Embase et la littérature grise pour recenser des études publiées entre le 1er janvier 2018 et le 18 février 2021 concernant l’utilisation du cannabis et ses effets sur l’infertilité, la contraception, les symptômes périménopausiques et postménopausiques et la douleur pelvienne. Toutes les publications des types suivants ont été incluses : essais cliniques, études observationnelles, revues (y compris les revues systématiques et les méta-analyses), directives cliniques et déclarations de conférences de consensus. Un survol des publications a été effectué pour en confirmer la pertinence. Les termes de recherche ont été définis à l’aide des termes MeSH (Medical Subject Headings) et mots clés (et variantes) suivants : cannabis, cannabinoids, marijuana, dexanabinol, dronabinol et tetrahydrocannabinol. À ces termes ont été combinés les termes suivants afin de cerner la santé des femmes : estrogen, estradiol, medroxyprogesterone acetate, vaginal contraception, oral contraceptives, fertilization, amenorrhea, oligomenorrhea, pelvic pain, dysmenorrhea, endometriosis, interstitial cystitis, vulvodynia et menopause. Méthodes de validation Les auteurs ont évalué la qualité des données probantes et la force des recommandations en utilisant l’approche d’évaluation, de développement et d’évaluation (GRADE). Voir l’annexe A en ligne (tableau A1 pour les définitions et tableau A2 pour l’interprétation des recommandations fortes et faibles). Professionnels concernés Tous les fournisseurs de soins de santé qui prodiguent des soins aux femmes. DÉCLARATIONS SOMMAIRES 1.Le cannabis est de plus en plus utilisé, et les femmes l’utilisent couramment pour des raisons récréatives et médicales (élevée). 2.L’utilisation de cannabis, en particulier des produits contenant du tétrahydrocannabinol, peut provoquer ou exacerber une psychose et aggraver une dépression (élevée). 3.Les résultats des études sur l’association entre le cannabis et l’anxiété sont contradictoires; par conséquent, cette association nécessite des recherches plus approfondies (élevée). 4.L’utilisation de cannabis, semblable à celle d’autres substances psychoactives, peut être associée à des comportements sexuels à risque élevé (faible). 5.Il n’existe aucunes données probantes indiquant que le cannabis altère l’efficacité des méthodes contraceptives (faible). 6.Les données probantes sont limitées concernant l’effet nocif de l’utilisation fréquente de cannabis sur la fertilité féminine (moyenne), mais l’utilisation fréquente peut diminuer la fertilité masculine (moyenne). 7.Il n’existe aucune donnée probante concernant l’utilisation de cannabis pour le traitement des symptômes périménopausiques (très faible). 8.Il n’existe aucune donnée probante indiquant que les produits de cannabis soulagent la douleur pelvienne chronique (faible). RECOMMANDATIONS 1.Il faut dépister l’utilisation de cannabis chez les femmes au même titre que pour toute autre consommation de substances psychoactives (forte, moyenne) et amorcer une exploration plus poussée de ses effets (forte, moyenne). 2.Il est possible de dépister l’utilisation de cannabis à l’aide d’outils de dépistage appropriés (conditionnelle, moyenne). 3.Il y a lieu d’adopter une approche de soins tenant compte des traumatismes et de miser sur la réduction des méfaits lorsqu’il s’agit de poser des questions sur l’utilisation de cannabis (forte, faible). 4.Le fait qu’une femme utilise du cannabis ne devrait pas influencer son choix de méthode contraceptive (forte, moyenne). 5.Les couples doivent être informés que l’utilisation de cannabis semble nuire à la fertilité masculine et pourrait avoir un effet nocif sur la fertilité féminine (conditionnelle, moyenne). 6.On doit caractériser les troubles du sommeil se manifestant en période périménopausique et essayer d’autres modes de traitement avant que les femmes ne puissent envisager l’utilisation de produits de cannabis pour cette indication (forte, moyenne). 7.Il y a lieu d’informer les femmes du manque de données probantes sur l’utilisation de produits de cannabis pour traiter la douleur pelvienne chronique (forte, moyenne).
Zusammenfassung Hintergrund Das Datenmaterial zur Verschreibung und therapeutischen Wirkung von medizinischen Cannabinoiden (CAM) im klinischen Alltag für ältere und geriatrische Patienten ist sehr beschränkt. Für diese Patienten rückt die Verordnung von CAM immer mehr in den therapeutischen Fokus. Ziel der Arbeit Erfassung der Patientencharakteristika und Verordnung (Verordnungsdauer, Dosierung) von CAM (Dronabinol, Nabiximols, Cannabisextrakte) und komedizierten Opioiden einer schmerztherapeutischen Praxis. Methoden Mit dem Stichtag 1. Juli 2020 wurde der Verbrauch von Opioiden (Morphinäquivalenz) und CAM-Tetrahydrocannabinol-Äquivalenz (THC-Äq.) für Männer bzw. Frauen und nach Alter analysiert. Ergebnisse 178 Schmerzpatienten wurden durchschnittlich (Median) 366 Tage (31 bis 2590 Tage) therapiert. Das Durchschnittsalter (Median) betrug 72 Jahre (26–96 Jahre); von den 115 Frauen (64,8 %) waren 34 jünger als 65 Jahre, 42 zwischen 65 und 80 Jahre und 40 über 80 Jahre alt; von den 63 Männern (35,2 %) waren 29 jünger als 65 Jahre, 24 zwischen 65 und 80 Jahre und 10 über 80 Jahre alt. Indikationen waren chronische Schmerzen und Einschränkungen der Lebensqualität. Von 1001 Verschreibungen waren 557 (55,6 %) Dronabinol als ölige Tropfen, 328 (32,7 %) Vollspektrumextrakte und 66 (6,6 %) Nabiximolsspray. 50 Rezepte (5 %) enthielten mehr als ein CAM simultan. Der Tagesverbrauch betrug im Median bei Dronabinolöl und Extrakten 9,6 mg THC, für Sprays 13,6 mg THC; er war bei Patienten > 64 Jahre konstant bzw. stieg bei jüngeren Patienten nichtsignifikant an. Frauen benötigten weniger THC als Männer (8,1 mg vs. 14,8 mg). 10 Patienten (5,6 %) brachen wegen fehlender Wirkung ab, 7 (3,9 %) wegen fehlender Kostenübernahme und nur 5 (2,8 %) wegen unerwünschter Arzneimittelwirkungen. 115 (65 %) Patienten erhielten gleichzeitig Opioide mit 65 Morphinäquivalenten/d im Median. Der Opioidverbrauch reduzierte sich signifikant um 24 Morphin-Äq./d (Median) bzw. 50 %, unabhängig von CAM-Dosis (< 7,5 oder > 7,5 mg THC-Äq./d), Geschlecht oder Alter. Diskussion Schmerzpatienten profitieren von einer lang dauernden Therapie mit CAM, die sicher und signifikant auch in niedriger Dosis den Opioidverbrauch senken. Frauen benötigen evtl. weniger THC als Männer. Nebenwirkungen von THC limitieren nicht einen Therapieversuch mit CAM im höheren und hohen Alter.
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Through the potency monitoring program at the University of Mississippi supported by National Institute on Drug Abuse (NIDA), a total of 18108 samples of cannabis preparations have been analyzed over the last decade, using a validated GC/FID method. The samples are classified as sinsemilla, marijuana, ditchweed, hashish, and hash oil (now referred to as cannabis concentrate). The number of samples received over the last 5 years has decreased dramatically due to the legalization of marijuana either for medical or for recreational purposes in many US states. The results showed that the mean Δ9-THC concentration has increased dramatically over the last 10 years, from 8.9% in 2008 to 17.1% in 2017. The mean Δ9-THC:CBD ratio also rose substantially from 23 in 2008 to 104 in 2017. There was also marked increase in the proportion of hash oil samples (concentrates) seized (0.5–4.7%) and their mean Δ9-THC concentration (6.7–55.7%) from 2008 to 2017. Other potency monitoring programs are also present in several European countries such as The Netherlands, United Kingdom, France, and Italy. These programs have also documented increases in Δ9-THC concentrations and Δ9-THC:CBD ratios in cannabis. These trends in the last decade suggest that cannabis is becoming an increasingly harmful product in the USA and Europe.
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Purpose of the review: Cannabis is the most commonly used illicit substance worldwide. In recent decades, highly concentrated products have flooded the market, and prevalence rates have increased. Gender differences exist in cannabis use, as men have higher prevalence of both cannabis use and cannabis use disorder (CUD), while women progress more rapidly from first use to CUD. This paper reviews findings from preclinical and human studies examining the sex-specific neurobiological underpinnings of cannabis use and CUD, and associations with psychiatric symptoms. Recent findings: Sex differences exist in the endocannabinoid system, in cannabis exposure effects on brain structure and function, and in the co-occurrence of cannabis use with symptoms of anxiety, depression and schizophrenia. In female cannabis users, anxiety symptoms correlate with larger amygdala volume and social anxiety disorder symptoms correlate with CUD symptoms. Female cannabis users are reported to be especially vulnerable to earlier onset of schizophrenia, and mixed trends emerge in the correlation of depressive symptoms with cannabis exposure in females and males. Summary: As prevalence of cannabis use may continue to increase given the shifting policy landscape regarding marijuana laws, understanding the neurobiological mechanisms of cannabis exposure in females and males is key. Examining these mechanisms may help inform future research on sex-specific pharmacological and behavioral interventions for women and men with high-risk cannabis use, comorbid psychiatric disease, and CUD.
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Objectives The study examined sex differences in trend and clinical characteristics of cannabis use disorder (CUD) diagnosis involved hospitalizations among adult patients. Methods We analyzed hospitalization data from the 2007–2011 Nationwide Inpatient Samples for patients aged 18–64 years (N = 15,114,930). Descriptive statistics were used to characterize demographic variables and to compare the proportions of CUD diagnosis and comorbid patterns between male and female hospitalizations. Logistic regressions were performed to examine the association of sex and other demographic variables with CUD diagnosis. Results During the study period, 3.3% of male and 1.5% of female hospitalizations had any-listed CUD diagnoses, and both sexes presented an upward trend in the number, rate, and proportion of CUD diagnosis. Among hospitalizations for patients aged 18–25 years, about 1 in 10 males and 1 in 20 females included a CUD diagnosis, and this proportion decreased with age strata. Mental disorders accounted for the highest proportion of CUD involved inpatient hospitalizations, and female CUD involved hospitalizations included a higher proportion of mental disorders that required hospitalized care compared with male hospitalizations (41% vs 36%). In each sex group, younger age, black race, lower household income, large metropolitan residence, non-private insurance, substance use diagnosis, and mental disorders were associated with elevated odds of having CUD diagnosis. Conclusion The large sample of clinical hospitalization data suggest an increased trend in CUD diagnosis and sex differences in several comorbidities with CUD-involved hospital admissions. Prevention and treatment for CUD should consider sex differences in clinical comorbidities.
Background: Although driving under the influence of cannabis is increasingly common among young adults, little is known about residual effects on driver behavior. This study examined acute and residual effects of smoked cannabis on simulated driving performance of young cannabis users. Methods: In this double-blind, placebo-controlled, parallel-group randomized clinical trial, cannabis users (1-4 days/week) aged 19-25 years were randomized with a 2:1 allocation ratio to receive active (12.5% THC) or placebo (0.009% THC) cannabis in a single 750 mg cigarette. A median split (based on whole-blood THC concentrations at the time of driving) was used to divide the active group into low and high THC groups. Our primary outcome was simulated driving performance, assessed 30 min and 24 and 48 h after smoking. Secondary outcomes included blood THC concentrations, subjective drug effects, and heart rate. Results: Ninety-six participants were randomized, and 91 were included in the final analysis (30 high THC, 31 low THC, 30 placebo). Mean speed (but not lateral control) significantly differed between groups 30 min after smoking cannabis (p ≤ 0.02); low and high THC groups decreased their speed compared to placebo. Heart rate, VAS drug effect and drug high increased significantly immediately after smoking cannabis and declined steadily after that. There was little evidence of residual effects in any of the measures. Conclusion: Acutely, cannabis caused decreased speed, increased heart rate, and increases in VAS drug effect and drug high. There was no evidence of residual effects on these measures over the two days following cannabis administration.
Currently, an unprecedented number of individuals can legally access cannabis. Vaporization is increasingly popular as a method to self-administer cannabis, partly due to perception of reduced harm compared with smoking. Few controlled laboratory studies of cannabis have used vaporization as a delivery method or evaluated the acute effects of cannabis among infrequent cannabis users. This study compared the concentrations of cannabinoids in whole blood and oral fluid after administration of smoked and vaporized cannabis in healthy adults who were infrequent users of cannabis. Seventeen healthy adults, with no past-month cannabis use, self-administered smoked or vaporized cannabis containing Δ9-tetrahydrocannabinol (THC) doses of 0, 10 and 25 mg in six double-blind outpatient sessions. Whole blood and oral fluid specimens were obtained at baseline and for 8 h after cannabis administration. Cannabinoid concentrations were assessed with enzyme-linked immunosorbent assay (ELISA) and liquid chromatography-tandem mass spectrometry (LC-MS-MS) methods. Sensitivity, specificity and agreement between ELISA and LC-MS-MS results were assessed. Subjective, cognitive performance and cardiovascular effects were assessed. The highest concentrations of cannabinoids in both whole blood and oral fluid were typically observed at the first time point (+10 min) after drug administration. In blood, THC, 11-OH-THC, THCCOOH and THCCOOH glucuronide concentrations were dose-dependent for both methods of administration, but higher following vaporization compared with smoking. THC was detected longer in oral fluid compared to blood and THCCOOH detection in oral fluid was rare and highly erratic. For whole blood, greater detection sensitivity for ELISA testing was observed in vaporized conditions. Conversely, for oral fluid, greater sensitivity was observed in smoked sessions. Blood and/ or oral fluid cannabinoid concentrations were weakly to moderately correlated with pharmacodynamic outcomes. Cannabis pharmacokinetics vary by method of inhalation and biological matrix being tested. Vaporization appears to be a more efficient method of delivery compared with smoking.
Background: Binding studies have demonstrated that levels of the cannabinoid receptor type-1 are highest in the basal ganglia and cerebellum, two areas critical for motor control. However, no studies have systematically examined the dose-related effects of intravenous delta-9-tetrahydrocannabinol, the primary cannabinoid receptor type-1 partial agonist in cannabis, on broad domains of psychomotor function in humans. Aims: Therefore, three domains of psychomotor function were assessed in former cannabis users (cannabis abstinent for a minimum of three months; n=23) in a three test-day, within-subject, double-blind, randomized, cross-over, and counterbalanced study during which they received intravenous delta-9-tetrahydrocannabinol (placebo, 0.015 mg/kg, and 0.03 mg/kg). Methods: Gross motor function was assessed via the Cambridge Neuropsychological Test Automated Battery Motor Screening Task, fine motor control via the Lafayette Instrument Grooved Pegboard task, and motor timing via a Paced Finger-Tapping Task. In addition, the Cambridge Neuropsychological Test Automated Battery Rapid Visual Processing Task was utilized to determine whether delta-9-tetrahydrocannabinol-induced motor deficits were confounded by disruptions in sustained attention. Results/outcomes: Delta-9-tetrahydrocannabinol resulted in robust dose-dependent deficits in fine motor control (Grooved Pegboard Task) and motor timing (Paced Finger-Tapping Task), while gross motor performance (Motor Screening Task) and sustained attention (Rapid Visual Processing Task) were unimpaired. Interestingly, despite the observed dose-dependent increases in motor impairment and blood levels of delta-9-tetrahydrocannabinol, subjects reported similar levels of intoxication in the two drug conditions. Conclusions/interpretation: These data suggest that while several domains of motor function are disrupted by delta-9-tetrahydrocannabinol, subjective feelings of intoxication are dissociable from cannabinoid-induced psychomotor effects. Results are discussed in terms of the potential neural mechanisms of delta-9-tetrahydrocannabinol in motor structures.
Recent policy changes have led to significant increases in the use of cannabis for both medical and recreational purposes. Although men are more likely to endorse past month cannabis use and are more frequently diagnosed with Cannabis Use Disorder relative to women, a growing proportion of medical cannabis users are reported to be women. The increased popularity of cannabis for medical purposes and the narrowing gap in prevalence of use between men and women raises questions regarding sex-dependent effects related to therapeutic efficacy and negative health effects of cannabis and cannabinoids. The objective of this review is to provide a translational perspective on the sex-dependent effects of cannabis and cannabinoids by synthesizing findings from preclinical and clinical studies focused on sex comparisons of their therapeutic potential and abuse liability, two specific areas that are of significant public health relevance. Hormonal and pharmacological mechanisms that may underlie sex differences in the effects of cannabis and cannabinoids are highlighted.
Objective: The objective of this study was to present current information on the prevalence, correlates, comorbidity and quality of life among men and women with cannabis use disorder (CUD). Methods: In 2012-2013, 36,309 respondents ≥18years old participated in face-to-face interviews in the National Epidemiologic Survey on Alcohol and Related Conditions-III. Results: Prevalence of 12-month CUD was greater among men (3.5%) than women (1.7%). Women experienced shorter duration from onset of cannabis use to onset of CUD than men (mean=5.8years, men; mean=4.7years, women). In both men and women, prevalences of CUD were greater among young adults, Blacks, and those with lower income and greater among Native American women relative to White women. CUD was highly comorbid with other substance use disorders, PTSD, ASPD and borderline and schizotypal PDs for men and women. Quality of life for individuals with CUD was low regardless of gender. Conclusions: DSM-5 CUD among men and women is highly prevalent, comorbid and characterized by low quality of life. Results highlighted the need for integrated treatment of CUD and comorbid disorders and the urgency of identifying and implementing effective prevention and intervention approaches, especially for those sociodemographic subgroups for which both men and women are at greater risk for the disorder.
Objective: Generally, cannabis use has been more prevalent in men than in women. However, emerging evidence suggests that the prevalence of cannabis use is converging among males and females from recent cohorts. This study aimed to systematically summarize published literature on birth cohort changes in male-to-female ratios in prevalence of cannabis use. Method: Twenty-two studies with a median sample size of 85,052 were identified for inclusion. Data were collected between 1979 and 2010, representing birth cohorts from 1936 to 1999. For quantitative synthesis, male-to-female ratios in prevalence of any cannabis use were calculated for all 5-year birth cohorts available, generating 348 separate ratios among birth cohorts from 1941 to 1995 in 30 countries. Random-effects meta-analyses generated pooled sex ratios, stratified by 5-year birth cohorts. Results: Of the 22 included studies, 10 reported some evidence of sex convergence in cannabis use among more recent cohorts. Quantitative synthesis found that the ratio of cannabis use prevalence in males and females decreased significantly from 2.0 among cohorts born in 1941 to 1.3 among those born in 1995. Conclusions: Findings support the narrowing sex gap in the prevalence of cannabis use. Results are concordant with a broader literature demonstrating sex convergence in prevalence of other substance use, particularly alcohol use and related harms. Both young women and men should be the target of prevention and early intervention efforts. Future research in more diverse global settings, especially in low- and middle-income countries, would enhance the international scope of the findings.
Background and objectives: Recent evidence suggests that women may fare worse than men in cannabis trials with pharmacologic interventions. Identifying baseline clinical profiles of treatment-seeking cannabis-dependent adults could inform gender-specific treatment planning and development. Methods: The current study compared baseline demographic, cannabis use, and psychiatric factors between women (n = 86) and men (n = 216) entering the Achieving Cannabis Cessation-Evaluating N-acetylcysteine Treatment (ACCENT) study, a multi-site, randomized controlled trial conducted within the National Drug Abuse Treatment Clinical Trials Network. Results: Women reported greater withdrawal intensity (p = .001) and negative impact of withdrawal (p = .001), predominantly due to physiological and mood symptoms. Women were more likely to have lifetime panic disorder (p = .038) and current agoraphobia (p = .022), and reported more days of poor physical health (p = .006) and cannabis-related medical problems (p = .023). Women reporting chronic pain had greater mean pain scores than men with chronic pain (p = .006). Men and women did not differ on any measures of baseline cannabis use. Discussion and conclusions: Cannabis-dependent women may present for treatment with more severe and impairing withdrawal symptoms and psychiatric conditions compared to cannabis-dependent men. This might help explain recent evidence suggesting that women fare worse than men in cannabis treatment trials of pharmacologic interventions. Baseline clinical profiles of treatment-seeking adults can inform gender-specific treatment planning and development. Scientific significance: Cannabis-dependent women may benefit from integrated treatment focusing on co-occurring psychiatric disorders and targeted treatment of cannabis withdrawal syndrome.(Am J Addict 2017;26:136-144).