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 ⌬ 9-tetrahydrocannabinol-rich (CAN THC) or cannabidiol-rich (CAN CBD) whole-plant cannabis extracts. Male Sprague-Dawley rats were trained to nose-poke for discrete puffs of CAN THC , CAN CBD , or vehicle (VEH) in daily 1 h sessions. Cannabis vapor reinforcement resulted in strong discrimination between active and inactive operanda. CAN THC maintained higher response rates under fixed ratio schedules and higher break points under progressive ratio schedules compared with CAN CBD 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 CAN THC administration decreased hippocampal CB1 receptor binding. Removal of CAN THC reinforcement (but not CAN CBD) 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.

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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.

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