Psychopharmacology
May 1, 2019
Thomas R. Arkell, Nicholas Lintzeris, Richard C. Kevin et al.
177 citations
Both THC-dominant and THC/CBD equivalent cannabis increased lane weaving during simulated driving but had little effect on other driving measures. Impairment on the Digit Symbol Substitution Task, Divided Attention Task, and Paced Auditory Serial Addition Task occurred with both active cannabis types, with worse performance on the latter two tasks after THC/CBD equivalent cannabis. Subjective feelings of being "stoned" and confidence in driving ability did not differ by CBD content. Peak plasma THC concentrations were higher after THC/CBD equivalent cannabis, suggesting a possible pharmacokinetic interaction. Cannabis with equivalent CBD and THC appears no less impairing than THC-dominant cannabis, and CBD may exacerbate THC-induced impairment in some circumstances.
Cannabis and Cannabinoid Research
April 2, 2018
Muhammad Waqas, Frederick S. Barrett, Nicolas J. Schlienz et al.
37 citations
A healthy 30-year-old man experienced auditory and visual hallucinations after inhaling vaporized cannabis containing 25 mg of THC in a controlled laboratory study. His scores on the Hallucinogen Rating Scale (HRS) were higher on the Volition, Intensity, Perception, and Somaesthesia subscales compared to maximum doses of cannabis, psilocybin, dextromethorphan, or salvinorin A from other studies. However, his Affect and Cognition subscale scores were lower than those for psilocybin and dextromethorphan, indicating the hallucinatory experience was qualitatively different from classic hallucinogens. The authors suggest cannabis-induced hallucinations may involve a unique pharmacological mechanism and should be considered as a potential adverse event in clinical cannabis use.
Adolescent psychiatry (Hilversum, Netherlands)
April 1, 2013
Ryan Vandrey, Matthew W Johnson, Patrick S Johnson et al.
26 citations
Over the past decade, non-medical use of novel drugs—including synthetic cannabinoids, synthetic cathinones, and the hallucinogen Salvia divinorum—has proliferated worldwide, sold over the counter and online as legal highs or substitutes for traditional illicit drugs. These substances, often first synthesized in academic or pharmaceutical labs, are not detected in routine drug screens and lack substance-specific treatments for toxicity. The review describes their epidemiology, toxicologic and pharmacological properties, and characteristic signs of misuse, recommending that clinicians use a symptom-specific treatment approach for each case.
JAMA Psychiatry
January 1, 2023
Brian D Kiluk, Bethea A Kleykamp, Sandra D Comer et al.
22 citations
A review sponsored by a public-private partnership addresses clinical trial design for new opioid use disorder (OUD) treatments that target systems other than the μ-opioid receptor. The authors present consensus recommendations for evaluating novel therapies such as cannabinoids, psychedelics, sedative-hypnotics, and immunotherapeutics. Key design elements include specifying the treatment stage (e.g., early abstinence, long-term recovery), defining the treatment's role (adjunctive or independent), selecting patient-informed primary outcomes that assess opioid use patterns, retention, and quality of life, and monitoring adverse events like relapse or overdose, especially when patients are not on maintenance opioid agonist or antagonist medications. Incorporating input from people with lived experience is urged to accelerate development and uptake of effective therapeutics.
Journal of Psychopharmacology
November 10, 2023
David Wolinsky, Frederick Streeter Barrett, Ryan Vandrey
16 citations
Cannabis, especially high-THC varieties, may be able to produce perceptual changes, aversiveness, and mystical experiences similar to those caused by classic psychedelics like psilocybin. Although cannabis is not typically regarded as having psychedelic effects in modern research, historical use alongside psychedelics suggests otherwise. The review finds that recent controlled studies may have failed to observe these effects due to the doses, set, and settings used. Further research is needed to test high doses of THC in therapeutic contexts similar to those used for psychedelics. If cannabis can reliably generate psychedelic experiences, it could be explored as an adjunctive treatment for psychiatric disorders and as an active comparator in clinical trials.
JAMA Network Open
May 1, 2026
C Austin Zamarripa, Spencer Lin, Mckenna Klausner et al.
Combining cannabis edibles with alcohol worsens driving impairment more than either substance alone. In a controlled experiment with 25 healthy adults who reported prior co-use, driving performance was significantly impaired under most active drug conditions, including 25 mg THC with alcohol at 0.05% breath alcohol concentration. The legal alcohol intoxication limit of 0.08% may be too high when cannabis has also been consumed. Standard field sobriety tests often failed to detect impairment that was evident in driving measures. The findings suggest a need for better impairment detection and policies that account for co-use.
Neuroscience and Biobehavioral Reviews
September 1, 2026
Isabella Goodwin, Dominic Oliver, Edward Chesney et al.
A meta-analysis of 41 double-blind, placebo-controlled experiments involving 1,020 infrequent cannabis users found that acute THC administration increases feelings of high, anxiety, and tiredness, while decreasing alertness and contentedness, with no effect on calmness. Inhaled THC dose-dependently increased high and contentedness but decreased calmness, with greater consistency in high and contentedness at higher doses. On a 100-point scale, inhaling 5 mg THC increased high by 34.3 points, anxiety by 14.4, tiredness by 26.3, and calmness by 4.5, while decreasing alertness by 40.2 and contentedness by 71.0. Oral THC showed no significant subjective effects, though higher oral doses produced more consistent alertness. These findings can inform public health guidance on expected THC effects.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
November 1, 2025
Justin C Strickland, Hayleigh E Tilton, Noah M Patton et al.
Caffeine co-administered with THC produced minimal changes in subjective effects, performance, or metabolism, though signals for perceived driving impairment were observed. In contrast, CBD co-administered with THC and caffeine increased outcomes associated with abuse liability and performance impairment versus THC alone. CBD also increased plasma THC and 11-OH-THC concentrations. These data provide the first direct assessment of pharmacodynamic and pharmacokinetic effects of THC and caffeine co-administered in humans, emphasizing the importance of considering full cannabinoid profiles and drug combinations in regulatory decision-making.