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.
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.