Psychedelics medicines have received a lot of attention recently. This is primarily because of the success in two of them, psilocybin and MDMA, in treating depression and post-traumatic stress disorder. These two psychedelics are the two that have been the most studied for their therapeutic properties and their basic science. There are more psychedelics such as LSD, mescaline, ayahuasca, DMT (dimethyltryptamine), ibogaine and the dissociative anesthetic ketamine, which have received less attention primarily because they do not currently offer a financial reward to pharmaceutical companies looking to develop these drugs for profit. When looking at the prospects of other drugs in this realm it is useful to break them down into the two types of psychedelics with different basic actions but similar end results.
What Are the Empathogens?
MDMA belongs to the psychedelic subclass of empathogens. This synthetic derivative of amphetamine acts on a range of neurotransmitters including dopamine, oxytocin, serotonin, and norepinephrine. This drug and others in its subclass promote empathy, interpersonal connectedness, trust and attachment as well as euphoria and a sense of meaning. The perceptual changes that MDMA and other empathogens produce are generally less intense than seen in classical psychedelics. As a rule, MDMA and its empathogen “cousins” make people slower to become angry and amplify positive emotional responses.

Physiological Effects of Empathogens
Different medicines have different side effects based on their chemical composition. While MDMA has been associated with drug deaths over decades of “street” use there have been no significant, dangerous problems in controlled clinical research settings. High blood pressure and a rapid pulse can happen with this psychedelic medicine as it is derived from the stimulant amphetamine. Other potential side effects are a low blood sodium level or hyponatremia, liver toxicity, and neurotoxicity. In the research setting there have been no reports of addictive or drug-seeking behavior. As we have noted, the pharmaceutical grade medicines used in research studies are given in appropriate doses and do not include the sorts of potentially dangerous additives seen in street drugs.
Classical Psychedelics
Psilocybin and other classical psychedelics share the trait of being antagonistic to the serotonin 5HT-2A receptor in the brain. Although there is some variation of effects within this group, classical psychedelics alter perception by amplifying what we experience, distorting reality, creating illusions, or causing outright hallucinations. They also cause intense emotions in some users and generally create greater cognitive flexibility. In higher doses some users experience mystical experiences, a sense of interconnectedness with others, and ego dissolution (an altered sense of oneself).

Side Effects of Classical Psychedelics
Anxiety and a general sense of dissatisfaction are sometimes seen in those who use classical psychedelics. As a group these drugs are tolerated well and in the numerous clinical trials with psilocybin a third of patients experienced headaches that were brief. One person experienced a short term blood pressure elevation. While nausea and vomiting are occasionally seen with psilocybin ingestion, serious neurological or cardiac problems have never been reported. In clinical trials no psychotic episodes have been reported. No suicide attempts have even been seen among those for whom psilocybin has been used in research studies.
Long term studies of people who have used classical psychedelics recreationally indicate that these substances are the safest of all recreational drugs with the lowest incidence of emergency room visits after use. Use of these substances over years is also associated with lower suicide rates than seen in the general population. Classical psychedelics do not cause physical dependence which is consistent with a virtually zero rate of drug abuse.
What the Two Types of Psychedelics Have in Common
Both classical psychedelics and empathogens change how people think and how they experience the world. The search for the specific aspect or aspects of these drugs that do the job in treating depression, PTSD, generalized anxiety, and substance abuse is ongoing. There is disagreement among researchers as to whether the mystical and hallucinatory effects are necessary or not. Attempts are underway to synthesize drugs that lack the mystical experiences but still help in treatment. What is uniform among all of these is that they help people reorient and reframe their beliefs which have been strongly held and are often damaging to their mental health.
Psychedelics in both categories are referred to as belief relaxers. Maladaptive beliefs or expectations are commonly a major factor in severe depression, PTSD, and even substance abuse. By causing belief “relaxation” these meds facilitate coaching and psychotherapy where new expectations and beliefs are created on the way to relieving depression and PTSD.