Cognitive test performance in chronic cannabis flower users, concentrate users, and non-users.

Extremely high-potency cannabis concentrates are becoming increasingly available and popular among consumers. While prior research indicates these products are perceived to have greater detrimental effects relative to cannabis flower, few studies have examined their relative objective effects, and no existing studies have compared the cognitive test performance of sober flower users, concentrate users, and non-users. A total of 198 healthy adults (98 non-users, 46 exclusive flower users, and 54 concentrate users) were administered a battery of tests of memory, psychomotor speed, attention, and executive functioning under sober laboratory-controlled conditions. Significant group differences were detected on tests of verbal free recall and episodic prospective memory, with both the flower users and concentrate users demonstrating significantly worse performance than non-users. Concentrate (but not flower) users performed worse than non-users on a measure of source memory, but contrary to our hypothesis, there were no significant differences between flower and concentrate users on any of the cognitive tests. Results indicate that, under sober conditions, individuals who regularly use concentrates are no more cognitively impacted than those who exclusively use flower. These null findings may reflect the tendency for concentrate users to self-titrate and use significantly lower quantities of concentrates than flower.

Pot at the End of the Rainbow: Cannabis Use Among Sexual Minorities.

Introduction: Gay, lesbian, and bisexual individuals (i.e., sexual minorities) use cannabis more frequently than heterosexuals; however, little research has directly compared sexual minorities' patterns of cannabis use (e.g., quantity, age of onset, forms of cannabis used) with heterosexuals. Some research has identified motivations for cannabis use in sexual minorities, but much of this research has been qualitative and/or narrow in scope (e.g., focused on sexual motivations). To the best of our knowledge, no previous research has used a validated measure to examine motives for cannabis use among sexual minorities. Additionally, cannabis use is known to be associated with mental health symptoms, but little research has examined relationships between cannabis use and mental health in this population. Materials and Methods: Data analyses were performed on archival survey data collected from 10 undergraduate psychology subject pools across the United States (N=4,669) as a part of Project ART (Addictions Research Team). Participants indicated their sexual orientation using a 5-point scale, and responses were used to classify participants into three groups: the majority of the sample (n=3,483) were classified into the heterosexual group, about one quarter were classified into the bisexual group (n=1,081), and a small number were classified into the gay group (n=105). Results: The bisexual group was more likely to report using cannabis. They also reported using cannabis more frequently, were more likely to report use of all product types (i.e., flower, concentrates, and edibles), and reported more severe symptoms of cannabis use disorder (CUD) than the heterosexual group. The bisexual group also reported higher levels of coping and enhancement motives for using cannabis and reported higher levels of all measured mental health symptoms (e.g., depression, suicidality, generalized anxiety, and social anxiety) compared with the heterosexual group. Conclusions: Increased frequency of cannabis use, use of a broad range of different products, and use of cannabis to cope with mental health concerns may be placing bisexual individuals at greater risk of CUD. Findings from this study can be used to guide future research and help target mental health interventions among bisexual individuals.

Estimating THC Consumption from Smoked and Vaped Cannabis Products in an Online Survey of Adults Who Use Cannabis.

Introduction: Quantification of consumption patterns of the primary psychoactive compounds in cannabis, which cause euphoria or intoxication, is sorely needed to identify potential risks and benefits of use and to provide meaningful safety information to the public. The diversity of products available, multiple methods of administration, and lack of labeling of products have made such quantification challenging. Our group is developing a survey instrument for estimating the quantity of delta 9-tetrahydrocannabinol (THC) consumed in population samples, which is flexible and incorporates individualized reports of patterns of consumption. This study provides an illustration of a procedure for translating self-reported consumption into milligrams of THC (mgTHC), which may serve as a working model for future quantification efforts. Methods: Social media advertising was leveraged to enroll 5627 adults who use cannabis into an online, anonymous survey study. Only those who used cannabis in the past 7 days, used flower or concentrate products, and who chose to report their quantity of use in hits per day or grams per week (n=3211) were included in this report. Formulas were used to estimate mgTHC used per day, in hits per day or grams per week; potency (%THC); constants for estimating the amount of material consumed for each hit; and a method of administration efficiency constant to account for THC loss due to the administration method. Results: The estimate for mgTHC used per day was M=92.8 mg/day (SD=97.2 mg; 1st-3rd quartile range=25-132 mg). The estimated quantity of use was much lower for those reporting in hits (M=43.7 mg, SD=43.8) than for those reporting in grams (M=115.1 mg, SD=107.0). The estimated rate of binge use in the past week, arbitrarily defined as more than 50 mgTHC within any one daily time quadrant, was 6.8%, which increased to 29.3% if 25 mgTHC was used. Conclusions: The approach illustrated in this study goes beyond existing cannabis measures by asking participants to provide highly detailed estimates of their past 7-day use patterns and then applying a logical formula to translate this information into mgTHC. This initial procedure has limitations and lacks generalization; however, we hope this demonstration stimulates testing of similar approaches and relevant laboratory experiments that will enhance the validity of cannabis consumption estimation procedures.

Self-Reported Effects of Cannabis on ADHD Symptoms, ADHD Medication Side Effects, and ADHD-Related Executive Dysfunction.

OBJECTIVE: People with ADHD are more likely to use cannabis but little is known about the effects of cannabis on ADHD symptoms, ADHD medication side effects, or ADHD-related executive dysfunction. METHOD: Students (n = 1,738) completed an online survey containing measures of ADHD symptoms, cannabis use, perceived effects of cannabis on ADHD symptoms and medication side effects, as well as executive dysfunction. RESULTS: Participants with ADHD who have used cannabis reported that cannabis has acute beneficial effects on many symptoms of ADHD (e.g., hyperactivity, impulsivity). Further, they perceived cannabis to improve most of their medication side effects (e.g., irritability, anxiety). Finally, cannabis use frequency was a significant moderator of the associations between symptom severity and executive dysfunction. CONCLUSION: Results suggest people with ADHD may be using cannabis to self-medicate for many of their symptoms and medication side effects and that more frequent use may mitigate ADHD-related executive dysfunction.

A Systematic Review and Meta-Analysis on the Effects of Exercise on the Endocannabinoid System.

Introduction: The endocannabinoid (eCB) system plays a key role in maintaining homeostasis, including the regulation of metabolism and stress responses. Chronic stress may blunt eCB signaling, and disruptions in eCB signaling have been linked to stress-related psychiatric disorders and physical health conditions, including anxiety, depression, post-traumatic stress disorder (PTSD), diabetes, and obesity. Pharmacological and nonpharmacological behavioral interventions (e.g., exercise) that target the eCB system may be promising therapeutic approaches for the prevention and treatment of stress-related diseases. In this study, we perform a systematic review and the first meta-analysis to examine the impact of exercise on circulating eCB concentrations. Materials and Methods: We performed a review of the MEDLINE (PubMed) database for original articles examining the impact of exercise on eCBs in humans and animal models. A total of 262 articles were screened for initial inclusion. Results: Thirty-three articles (reporting on 57 samples) were included in the systematic review and 10 were included in the meta-analysis. The majority of samples that measured anandamide (AEA) showed a significant increase in AEA concentrations following acute exercise (74.4%), whereas effects on 2-arachidonoylglycerol (2-AG) were inconsistent. The meta-analysis, however, revealed a consistent increase in both AEA and 2-AG following acute exercise across modalities (e.g., running, cycling), species (e.g., humans, mice), and in those with and without pre-existing health conditions (e.g., PTSD, depression). There was substantial heterogeneity in the magnitude of the effect across studies, which may relate to exercise intensity, physical fitness, timing of measurement, and/or fasted state. Effects of chronic exercise were inconsistent. Conclusions: Potential interpretations and implications of exercise-induced mobilization of eCBs are discussed, including refilling of energy stores and mediating analgesic and mood elevating effects of exercise. We also offer recommendations for future work and discuss therapeutic implications for exercise in the prevention and treatment of stress-related psychopathology.

A Large-Scale Naturalistic Examination of the Acute Effects of Cannabis on Pain.

Introduction: Cannabis use for pain relief is commonly reported, yet laboratory studies and clinical trials suggest that cannabinoids are weak analgesics, and it is unclear whether perceived reductions in pain from before to after cannabis use relate to factors such as dose, method of administration, phytocannabinoid content, or the age or gender of the user. We determined whether inhalation of cannabis decreased self-reported pain ratings as well as whether user gender, age, time, method of administration, tetrahydrocannabinol (THC)/cannabidiol (CBD) content, or dose of cannabis contribute to changes in these ratings. We also examined whether tolerance may develop to the analgesic effects of cannabis over time. Materials and Methods: Archival data were obtained from Strainprint®, a medical cannabis app that allows patients to track symptoms before and after using different strains and doses of cannabis. Latent change score models and multilevel models were used to analyze data from 131,582 sessions in which inhaled cannabis was used to treat "muscle pain," "joint pain," or "nerve pain." Results: For all three pain symptoms, severity ratings decreased significantly after cannabis use. Women reported higher baseline and postcannabis pain severity than did men, and men reported larger decreases in pain than did women. Neither THC nor CBD content nor their interaction predicted reductions in pain ratings. However, vaping was associated with larger reductions in joint pain ratings than was smoking, and lower doses were associated with larger reductions in nerve pain ratings. Additionally, for all three pain symptoms, the dose of cannabis used to manage pain increased significantly over time. Conclusions: Inhaled cannabis reduces self-reported pain severity by ∼42-49%. However, these reductions appear to diminish across time, and patients use larger doses across time, suggesting that analgesic tolerance develops with continued use.

Survey of Patients Employing Cannabigerol-Predominant Cannabis Preparations: Perceived Medical Effects, Adverse Events, and Withdrawal Symptoms.

Introduction: Cannabigerol (CBG), and its precursor before decarboxylation, cannabigerolic acid is sometimes labeled the "mother of all cannabinoids." The purpose of the present study was to investigate reasons for use and self-reported therapeutic effects in CBG-predominant cannabis users. Usage patterns and adverse effects, including withdrawal symptoms were also explored. Methods: Cannabidiol-predominant cannabis users were recruited online to complete an online survey assessing CBG use patterns, conditions treated with CBG-predominant cannabis (containing >50% CBG), perceived efficacy, associated adverse events, and withdrawal symptoms. One hundred twenty-seven eligible participants (U.S. residents ages 21+ who reported using CBG-predominant cannabis in the past 6 months) completed the survey. Results: Most of the samples (n=65; 51.2%) reported use of CBG-predominant products solely for medical purposes (n=46; 36.2% reported use for medical and recreational purposes; n=8; 6.3% reported recreational use only, and n=8 were missing). The most common conditions the complete sample reported using CBG to treat were anxiety (51.2%), chronic pain (40.9%), depression (33.1%), and insomnia/disturbed sleep (30.7%). Efficacy was highly rated, with the majority reporting their conditions were "very much improved" or "much improved" by CBG. Furthermore, 73.9% claimed superiority of CBG-predominant cannabis over conventional medicines for chronic pain, 80% for depression, 73% for insomnia, and 78.3% for anxiety. Forty-four percent of CBG-predominant cannabis users reported no adverse events, with 16.5% noting dry mouth, 15% sleepiness, 11.8% increased appetite, and 8.7% dry eyes. Around 84.3% reported no withdrawal symptoms, with sleep difficulties representing the most frequently endorsed withdrawal symptom (endorsed by two respondents). Conclusions: This is the first patient survey of CBG-predominant cannabis use to date, and the first to document self-reported efficacy of CBG-predominant products, particularly for anxiety, chronic pain, depression, and insomnia. Most respondents reported greater efficacy of CBG-predominant cannabis over conventional pharmacotherapy, with a benign adverse event profile and negligible withdrawal symptoms. This study establishes that humans are employing CBG and suggests that CBG-predominant cannabis-based medicines should be studied in randomized controlled trials.

A review of the effects of acute and chronic cannabinoid exposure on the stress response.

While cannabis has been used for centuries for its stress-alleviating properties, the effects of acute and chronic cannabinoid exposure on responses to stress remain poorly understood. This review provides an overview of studies that measured stress-related endpoints following acute or chronic cannabinoid exposure in humans and animals. Acute cannabinoid exposure increases basal concentrations of stress hormones in rodents and humans and has dose-dependent effects on stress reactivity in humans and anxiety-like behavior in rodents. Chronic cannabis exposure is associated with dampened stress reactivity, a blunted cortisol awakening response (CAR), and flattened diurnal cortisol slope in humans. Sex differences in these effects remain underexamined, with limited evidence for sex differences in effects of cannabinoids on stress reactivity in rodents. Future research is needed to better understand sex differences in the effects of cannabis on the stress response, as well as downstream impacts on mental health and stress-related disorders.

Acute effects of high-potency cannabis flower and cannabis concentrates on everyday life memory and decision making.

Statewide legislation has increased public access to high-potency cannabis flower and concentrates, yet federal restrictions limit researchers' access to relatively low-potency whole-plant cannabis. The goal of this study was to examine the acute effects of high-potency cannabis on cognition using a novel methodology. We further sought to compare cognitive effects of high-potency cannabis flower with and without cannabidiol (CBD), as well as cannabis concentrates to cannabis flower. 80 cannabis users were randomly assigned to stay sober or use their funds to purchase one of three high-potency cannabis products: (1) high-potency flower (≥ 20% THC) without CBD, (2) high-potency flower with CBD, (3) high-potency concentrates (≥ 60% THC) with CBD. Participants were observed over Zoom videoconferencing while inhaling their product or remaining sober and then were administered tests of everyday life memory (prospective, source, temporal order, and false memory) and decision making (risky choice framing, consistency in risk perception, resistance to sunk cost, and over/under confidence) over Zoom. High-potency cannabis flower with CBD impaired free recall, high-potency flower without CBD and concentrates had detrimental effects on source memory, and all three products increased susceptibility to false memories. CBD did not offset impairments and concentrates were self-titrated producing comparable intoxication and impairment as flower.

Differences in cortisol following cooperative and competitive work-related tasks with same-sex versus opposite-sex partners.

Previous research indicates that circulating concentrations of cortisol increase during interactions with opposite-sex others in the presence of mating cues. However, it remains unknown whether this phenomenon extends to work-related tasks in which explicit mating cues are absent. In a series of two studies, we assessed women's and men's salivary cortisol concentrations before and after completing a cooperative brainstorming (Study 1) and competitive negotiation (Study 2) task wherein they worked with same- or opposite-sex partners. Both studies revealed significant participant sex by partner sex interactions. Specifically, male participants demonstrated significantly larger increases in salivary cortisol concentrations when working alongside opposite-sex as opposed to same-sex partners on a cooperative task. In contrast, female participants demonstrated significantly larger increases in salivary cortisol concentrations when working with opposite-sex as opposed to same-sex partners on a competitive task. Opposite-sex teams also produced fewer novel ideas relative to same-sex teams on the cooperative brainstorming task; however, differences in cortisol did not account for this effect. Our research extends previous research demonstrating elevated cortisol during opposite-sex interactions in the presence of explicit mating cues to a work-related context that is divorced from mating cues.

Acute Effects of Cannabis on Symptoms of Obsessive-Compulsive Disorder.

BACKGROUND: Little is known about the the acute effects of cannabis on symptoms of OCD in humans. Therefore, this study sought to: 1) examine whether symptoms of OCD are significantly reduced after inhaling cannabis, 2) examine predictors (gender, dose, cannabis constituents, time) of these symptom changes and 3) explore potential long-term consequences of repeatedly using cannabis to self-medicate for OCD symptoms, including changes in dose and baseline symptom severity over time. METHOD: Data were analyzed from the app Strainprint® which provides medical cannabis patients a means of tracking changes in symptoms as a function of different doses and strains of cannabis across time. Specifically, data were analyzed from 87 individuals self-identifying with OCD who tracked the severity of their intrusions, compulsions, and/or anxiety immediately before and after 1,810 cannabis use sessions spanning a period of 31 months. RESULTS: Patients reported a 60% reduction in compulsions, a 49% reduction in intrusions, and a 52% reduction in anxiety from before to after inhaling cannabis. Higher concentrations of CBD and higher doses predicted larger reductions in compulsions. The number of cannabis use sessions across time predicted changes in intrusions, such that later cannabis use sessions were associated with smaller reductions in intrusions. Baseline symptom severity and dose remained fairly constant over time. LIMITATIONS: The sample was self-selected, self-identified as having OCD, and there was no placebo control group. CONCLUSIONS: Inhaled cannabis appears to have short-term beneficial effects on symptoms of OCD. However, tolerance to the effects on intrusions may develop over time.

Endocannabinoids and related lipids in serum from patients with amyotrophic lateral sclerosis.

BACKGROUND: The goals of this study were to determine whether serum concentrations of endocannabinoids (eCB) and related lipids predict disease status in patients with amyotrophic lateral sclerosis (ALS) relative to healthy controls, and whether concentrations correlate with disease duration and severity. METHODS: Serum concentrations of the eCBs 2-arachidonoylglycerol (2-AG) and N-arachidonoylethanolamine (AEA), and related lipids palmitoylethanolamine (PEA), oleoylethanolamine (OEA), and 2-oleoylglycerol (2-OG), were measured in samples from 47 patients with ALS and 19 healthy adults. Hierarchical binary logistic and linear regression analyses assessed whether lipid concentrations predicted disease status (ALS or healthy control), duration, or severity. RESULTS: Binary logistic regression revealed that, after controlling for age and gender, 2-AG, 2-OG and AEA concentrations were unique predictors of the presence of ALS, demonstrating odds ratios of 0.86 (P = .039), 1.03 (P = .023), and 42.17 (P = .026), respectively. When all five lipids and covariates (age, sex, race, ethnicity, body mass index, presence of a feeding tube) were included, the resulting model had an overall classification accuracy of 92.9%. Hierarchical linear regression analyses indicated that in patients with ALS, AEA and OEA inversely correlated with disease duration (P = .030 and .031 respectively), while PEA demonstrated a positive relationship with disease duration (P = .013). None of the lipids examined predicted disease severity. CONCLUSIONS: These findings support previous studies indicating significant alterations in concentrations of circulating lipids in patients with ALS. They suggest that arachidonic and oleic acid containing small lipids may serve as biomarkers for identifying the presence and duration of this disease.

Cannabis vapor self-administration elicits sex- and dose-specific alterations in stress reactivity in rats.

RATIONALE: Cannabis users frequently report stress relief as their primary reason for use. Recent studies indicate that human cannabis users exhibit blunted stress reactivity; however, it is unknown whether this is a cause or a consequence of chronic cannabis use. OBJECTIVES: To determine whether chronic cannabis vapor self-administration elicits sex- and/or dose-dependent alterations in stress reactivity and basal corticosterone (CORT) concentrations, or whether pre-vapor exposure stress reactivity predicts rates of cannabis vapor self-administration. METHODS: Male and female rats were subjected to 30 min acute restraint stress to assess stress reactivity prior to vapor self-administration. Rats were then trained to self-administer cannabis extract vapor containing 69.9% Δ9-tetrahydrocannabinol (THC) at one of four extract concentrations (0, 75, 150, or 300 mg/ml) daily for 30 days. Half of the rats were then subjected to a second restraint stress challenge 24 h after the final self-administration session, while the other half served as no-stress controls. Plasma CORT concentrations were measured prior to stress and immediately post-stress offset. RESULTS: Female rats earned significantly more vapor deliveries than male rats. Pre-vapor stress reactivity was not a predictor of self-administration rates in either sex. Basal CORT concentrations were increased following vapor self-administration relative to pre-vapor assessment, irrespective of treatment condition. Importantly, cannabis self-administration dose-dependently reduced stress reactivity in female, but not male, rats. CONCLUSIONS: These data indicate that chronic cannabis use can significantly dampen stress reactivity in female rats and further support the use of the cannabis vapor self-administration model in rats of both sexes.

Short and Long-Term Effects of Cannabis on Symptoms of Post-Traumatic Stress Disorder.

BACKGROUND: Many individuals use cannabis to manage symptoms of post-traumatic stress disorder (PTSD), and evidence indicates that the endocannabinoid system represents a viable target for treating these symptoms. METHOD: Data from 404 medical cannabis users who self-identified as having PTSD were obtained from Strainprint®, a medical cannabis app that patients use to track changes in symptoms as a function of different strains and doses of cannabis across time. This sample collectively used the app 11,797 times over 31 months to track PTSD-related symptoms (intrusive thoughts, flashbacks, irritability, and/or anxiety) immediately before and after inhaling cannabis. Latent change score models were used to examine changes in symptom severity and predictors of these changes (gender, dose, cannabis constituents, time). Multilevel models were used to explore long-term consequences of repeatedly using cannabis to manage these symptoms. RESULTS: All symptoms were reduced by more than 50% immediately after cannabis use. Time predicted larger decreases in intrusions and irritability, with later cannabis use sessions predicting greater symptom relief than earlier sessions. Higher doses of cannabis predicted larger reductions in intrusions and anxiety, and dose used to treat anxiety increased over time. Baseline severity of all symptoms remained constant across time. LIMITATIONS: The sample was self-selected, self-identified as having PTSD, and there was no placebo control group. CONCLUSIONS: Cannabis provides temporary relief from PTSD-related symptoms. However, it may not be an effective long-term remedy as baseline symptoms were maintained over time and dose used for anxiety increased over time, which is indicative of development of tolerance.

The latent structure of cannabis misuse: A taxometric analysis.

Taxometric research on substance use problems has yielded inconsistent results, with some studies yielding evidence of a taxonic (categorical) latent structure and other studies yielding dimensional findings. The 2 previous studies that specifically examined cannabis misuse supported a dimensional latent structure. However, given the inconsistent findings for other substance use disorders and the changing legal status of, attitudes about, and patterns of cannabis use, the present study examined the latent structure of cannabis misuse in an attempt to replicate these previous findings. Participants were 804 cannabis using college students who completed measures of cannabis use anonymously online to reduce response biases. Consistent with previous research, the taxometric analyses yielded clear evidence that cannabis misuse has a dimensional latent structure. Furthermore, compared to a dichotomous measure of cannabis misuse, continuous measures of cannabis misuse were significantly more strongly associated with external correlates of cannabis misuse (e.g., stress). These findings have implications for the assessment, treatment, and study of cannabis use disorder. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

A Comprehensive Examination of the Links between Cannabis Use and Motivation.

Background: Cannabis use is widely perceived to produce an "amotivational syndrome" characterized by reduced desire to work or compete, passivity, and lower achievement orientation. The notion that cannabis diminishes motivation has been perpetuated in popular culture, despite the equivocal results of past research. Moreover, previous literature has largely failed to consider the potentially confounding influences of depression, other substance use, and personality, despite known relationships between these variables and cannabis use.Purpose: The purpose of this study was to elucidate the nature of the relationships between specific aspects of motivation and cannabis use/misuse. Moreover, we sought to determine whether depression, alcohol and other substance use, and/or personality could account for these relationships.Method: A total of 1,168 participants completed a survey comprising self-report measures of motivation (self-efficacy, apathy, goal orientation, reward-sensitivity, and behavioral inhibition/approach systems) and cannabis use/misuse (cannabis use status, cannabis use frequency, quantity, age of onset of cannabis use, symptoms of cannabis use disorder, problematic cannabis use).Results: The results revealed small (r < .30) but significant correlations between various aspects of cannabis use and motivation, which were largely accounted for by cannabis-related differences in depression, alcohol and other substance use, and personality. However, relationships between cannabis misuse and apathy remained statistically significant after controlling for confounds, indicating that individuals who misuse cannabis may demonstrate higher levels of apathy specifically.Conclusion: Collectively, these results suggest that differences in depression, substance use, and personality between cannabis users and non-users largely explain differences in motivation between these groups.

Vaporized Cannabis Extracts Have Reinforcing Properties and Support Conditioned Drug-Seeking Behavior in Rats.

Recent trends in cannabis legalization have increased the necessity to better understand the effects of cannabis use. Animal models involving traditional cannabinoid self-administration approaches have been notoriously difficult to establish and differences in the drug used and its route of administration have limited the translational value of preclinical studies. To address this challenge in the field, we have developed a novel method of cannabis self-administration using response-contingent delivery of vaporized Δ9-tetrahydrocannabinol-rich (CANTHC) or cannabidiol-rich (CANCBD) whole-plant cannabis extracts. Male Sprague-Dawley rats were trained to nose-poke for discrete puffs of CANTHC, CANCBD, or vehicle (VEH) in daily 1 h sessions. Cannabis vapor reinforcement resulted in strong discrimination between active and inactive operanda. CANTHC maintained higher response rates under fixed ratio schedules and higher break points under progressive ratio schedules compared with CANCBD or VEH, and the number of vapor deliveries positively correlated with plasma THC concentrations. Moreover, metabolic phenotyping studies revealed alterations in locomotor activity, energy expenditure, and daily food intake that are consistent with effects in human cannabis users. Furthermore, both cannabis regimens produced ecologically relevant brain concentrations of THC and CBD and CANTHC administration decreased hippocampal CB1 receptor binding. Removal of CANTHC reinforcement (but not CANCBD) resulted in a robust extinction burst and an increase in cue-induced cannabis-seeking behavior relative to VEH. These data indicate that volitional exposure to THC-rich cannabis vapor has bona fide reinforcing properties and collectively support the utility of the vapor self-administration model for the preclinical assessment of volitional cannabis intake and cannabis-seeking behaviors.SIGNIFICANCE STATEMENT The evolving legal landscape concerning recreational cannabis use has increased urgency to better understand its effects on the brain and behavior. Animal models are advantageous in this respect; however, current approaches typically used forced injections of synthetic cannabinoids or isolated cannabis constituents that may not capture the complex effects of volitional cannabis consumption. We have developed a novel model of cannabis self-administration using response-contingent delivery of vaporized cannabis extracts containing high concentrations of Δ9 tetrahydrocannabinol (THC) or cannabidiol. Our data indicate that THC-rich cannabis vapor has reinforcing properties that support stable rates of responding and conditioned drug-seeking behavior. This approach will be valuable for interrogating effects of cannabis and delineating neural mechanisms that give rise to aberrant cannabis-seeking behavior.

Overbaked: assessing and predicting acute adverse reactions to Cannabis.

BACKGROUND: Trends toward legalizing cannabis may increase experimentation with the drug among less experienced users with limited knowledge of possible adverse reactions. This study explores the prevalence, frequency, and levels of distress produced by various acute adverse reactions to cannabis, as well as predictors of these reactions. METHODS: The Adverse Reactions Scale (ARS) was created and administered to a large sample of undergraduate college students (n = 999) who were predominantly white (> 70%), female (> 70%), recreational (> 90%) cannabis users. The ARS was administered in an anonymous online survey measuring demographics, cannabis use patterns, cannabis use motives, personality, and negative affect. RESULTS: The most prevalent adverse reactions to cannabis were coughing fits, anxiety, and paranoia, which > 50% of the sample reported experiencing. The most frequently occurring reactions were coughing fits, chest/lung discomfort, and body humming, which occurred on approximately 30-40% of cannabis use sessions. Panic attacks, fainting, and vomiting were rated as the most distressing, with mean ratings falling between "moderately" and "quite" distressing. Multiple regression analyses revealed that lower frequency of cannabis use predicted increased frequency of adverse reactions. Symptoms of cannabis use disorder, conformity motives, and anxiety sensitivity were significant predictors of both the prevalence of, and distress caused by, adverse reactions. CONCLUSIONS: Relative to past research, this study provides a more comprehensive account of possible adverse reactions to cannabis, and individual difference variables that predict these reactions. This study has implications for inexperienced cannabis users, as well as medical professionals and budtenders who provide information about cannabis use.

Short- and Long-Term Effects of Cannabis on Headache and Migraine.

Use of cannabis to alleviate headache and migraine is relatively common, yet research on its effectiveness remains sparse. We sought to determine whether inhalation of cannabis decreases headache and migraine ratings as well as whether gender, type of cannabis (concentrate vs flower), delta-9-tetrahydrocannabinol, cannabidiol, or dose contribute to changes in these ratings. Finally, we explored evidence for tolerance to these effects. Archival data were obtained from Strainprint, a medical cannabis app that allows patients to track symptoms before and after using different strains and doses of cannabis. Latent change score models and multilevel models were used to analyze data from 12,293 sessions where cannabis was used to treat headache and 7,441 sessions where cannabis was used to treat migraine. There were significant reductions in headache and migraine ratings after cannabis use. Men reported larger reductions in headache than women and use of concentrates was associated with larger reductions in headache than flower. Further, there was evidence of tolerance to these effects. PERSPECTIVE: Inhaled cannabis reduces self-reported headache and migraine severity by approximately 50%. However, its effectiveness appears to diminish across time and patients appear to use larger doses across time, suggesting tolerance to these effects may develop with continued use.

Motives Matter: Cannabis use motives moderate the associations between stress and negative affect.

Young adults in the U.S. report high levels of stress which are known to contribute to depression and anxiety. Regular cannabis users frequently cite coping with stress as their primary motivation for use. However, research indicates that coping motives are associated with potentially negative outcomes, including cannabis-related problems and negative affect. Therefore, the theoretical rationale for the present study is that using cannabis to cope with stress may be maladaptive as it may exacerbate the same problems users are trying to ameliorate. That is, using cannabis to cope may potentiate links between stress and negative affect. We therefore sought to investigate whether cannabis use motives moderate the associations between stress and negative affect. A sample of 988 cannabis using college students completed an anonymous online survey containing measures of cannabis use, cannabis use motives, stress, depression, and anxiety. Correlation analyses revealed significant positive relationships between these variables. Moderation analyses indicated that coping motives was a significant moderator of the relationship between stress and depression, controlling for anxiety. In contrast, expansion and conformity motives were significant moderators of the relationship between stress and anxiety, controlling for depression. While cannabis may provide temporary relief from symptoms of stress, depression, and anxiety, using cannabis to cope may be related to higher levels of depression, and use of cannabis for expansion and conformity may be related to higher levels of anxiety. These findings have practical implications and contribute to emerging evidence demonstrating that motives for cannabis use may predict differential mental health outcomes.