An age-period-cohort analysis of trends in psychedelic and ecstasy use in the Australian population

The purpose of this paper is to provide an integrative review and offer novel insights regarding human research with classic psychedelics (classic hallucinogens), which are serotonin 2A receptor (5-HT2AR) agonists such as lysergic acid diethylamide (LSD), mescaline, and psilocybin. Classic psychedelics have been administered as sacraments since ancient times. They were of prominent interest within psychiatry and neuroscience in the 1950s to 1960s, and during this time contributed to the emergence of the field of molecular neuroscience. Promising results were reported for treatment of both end-of-life psychological distress and addiction, and classic psychedelics served as tools for studying the neurobiological bases of psychological disorders. Moreover, classic psychedelics were shown to occasion mystical experiences, which are subjective experiences reported throughout different cultures and religions involving a strong sense of unity, among other characteristics. However, the recreational use of classic psychedelics and their association with the counterculture prompted an end to human research with classic psychedelics in the early 1970s. We provide the most comprehensive review of epidemiological studies of classic psychedelics to date. Notable among these are a number of studies that have suggested the possibility that nonmedical naturalistic (non-laboratory) use of classic psychedelics is associated with positive mental health and prosocial outcomes, although it is clear that some individuals are harmed by classic psychedelics in non-supervised settings. We then review recent therapeutic studies suggesting efficacy in treating psychological distress associated with life-threatening diseases, treating depression, and treating nicotine and alcohol addictions. We also describe the construct of mystical experience, and provide a comprehensive review of modern studies investigating classic psychedelic-occasioned mystical experiences and their consequences. These studies have shown classic psychedelics to fairly reliably occasion mystical experiences. Moreover, classic-psychedelic-occasioned mystical experiences are associated with improved psychological outcomes in both healthy volunteer and patient populations. Finally, we review neuroimaging studies that suggest neurobiological mechanisms of classic psychedelics. These studies have also broadened our understanding of the brain, the serotonin system, and the neurobiological basis of consciousness. Overall, these various lines of research suggest that classic psychedelics might hold strong potential as therapeutics, and as tools for experimentally investigating mystical experiences and behavioral-brain function more generally.

3,4-Methylenedioxymethamphetamine (MDMA, 'ecstasy') releases serotonin and norepinephrine. MDMA is reported to produce empathogenic and prosocial feelings. It is unknown whether MDMA in fact alters empathic concern and prosocial behavior. We investigated the acute effects of MDMA using the Multifaceted Empathy Test (MET), dynamic Face Emotion Recognition Task (FERT) and Social Value Orientation (SVO) test. We also assessed effects of MDMA on plasma levels of hormones involved in social behavior using a placebo-controlled, double-blind, random-order, cross-over design in 32 healthy volunteers (16 women). MDMA enhanced explicit and implicit emotional empathy in the MET and increased prosocial behavior in the SVO test in men. MDMA did not alter cognitive empathy in the MET but impaired the identification of negative emotions, including fearful, angry and sad faces, in the FERT, particularly in women. MDMA increased plasma levels of cortisol and prolactin, which are markers of serotonergic and noradrenergic activity, and of oxytocin, which has been associated with prosocial behavior. In summary, MDMA sex-specifically altered the recognition of emotions, emotional empathy and prosociality. These effects likely enhance sociability when MDMA is used recreationally and may be useful when MDMA is administered in conjunction with psychotherapy in patients with social dysfunction or post-traumatic stress disorder.