Taking very low, repeated doses of psychedelics like LSD, psilocybin, mescaline, DMT, or MDMA may pose a risk of valvular heart disease because these substances activate the serotonin 5-HT2B receptor, which is linked to heart valve damage. All five compounds and some of their metabolites bind to this receptor with potency equal to or greater than their binding to the 5-HT2A receptor. Safety margins based on typical microdose blood levels are higher than those of known valvulopathogens, but risk is not absent. No animal or clinical studies properly designed to assess this risk exist for the psychedelics, though chronic full-dose MDMA use is associated with valvular heart disease. Further research is needed.
A clinical trial tested whether cannabidiol (CBD) can reduce the adverse effects of tetrahydrocannabinol (THC) and improve its tolerability as an analgesic. Healthy volunteers received THC alone or with different doses of CBD. Contrary to expectations, the highest CBD dose (450 mg) significantly increased THC's subjective, psychomotor, cognitive, and autonomous effects—for example, feeling high increased by 60.5%—and did not enhance pain relief. Lower CBD doses had no significant effect on THC's effects. CBD also increased blood levels of THC and its active metabolite. The findings do not support using CBD to reduce oral THC's adverse effects or to improve its analgesic properties.
Delta-8-THC, an intoxicating cannabinoid, has rapidly grown in use. This review summarizes decades of pharmacological studies on delta-8-THC, including receptor binding, cell signaling, animal and human activity, and pharmacokinetics, with special focus on comparisons to delta-9-THC. The pharmacokinetics and pharmacodynamics of the two isomers are very similar. Delta-8-THC is a partial agonist of the CB1 receptor and has cannabimimetic activity in both animals and humans. Its reduced potency in clinical studies compared to delta-9-THC can be explained by weaker CB1 receptor affinity, though other mechanisms may contribute. Gaps in knowledge, particularly in human studies, are highlighted.