OPEN Foundation

Day: 4 June 2014

Pharmacology of Hallucinations: Several Mechanisms for One Single Symptom?

Abstract

Hallucinations are complex misperceptions, that principally occur in schizophrenia or after intoxication induced by three main classes of drugs: psychostimulants, psychedelics, and dissociative anesthetics. There are at least three different pharmacological ways to induce hallucinations: (1) activation of dopamine D2 receptors (D2Rs) with psychostimulants, (2) activation of serotonin 5HT2A receptors (HT2ARs) with psychedelics, and (3) blockage of glutamate NMDA receptors (NMDARs) with dissociative anesthetics. In schizophrenia, the relative importance of NMDAR and D2R in the occurrence of hallucinations is still debated. Slight clinical differences are observed for each etiology. Thus, we investigated whether the concept of hallucination is homogenous, both clinically and neurobiologically. A narrative review of the literature is proposed to synthesize how the main contributors in the field have approached and tried to solve these outstanding questions. While some authors prefer one explanatory mechanism, others have proposed more integrated theories based on the different pharmacological psychosis models. In this review, such theories are discussed and faced with the clinical data. In addition, the nosological aspects of hallucinations and psychosis are addressed. We suggest that if there may be common neurobiological pathways between the different pharmacological systems that are responsible for the hallucinations, there may also be unique properties of each system, which explains the clinical differences observed.

Rolland, B., Jardri, R., Amad, A., Thomas, P., Cottencin, O., & Bordet, R. (2014). Pharmacology of Hallucinations: Several Mechanisms for One Single Symptom? Biomed Research International. http://dx.doi.org/10.1155/2014/307106
Link to full text

In Memoriam Alexander ‘Sasha’ Shulgin

With great sadness, the OPEN foundation would like to acknowledge the death of maverick chemist Alexander “Sasha” Shulgin, who passed away on June 2nd. Dubbed “the godfather of Ecstasy,” Shulgin was credited with introducing MDMA to psychologists in the late 70’s, years before the drug hit the global dance scene.

However MDMA was only one of hundreds of chemicals Shulgin synthesized during his lengthy career. After earning his biochemistry degree from UC Berkeley in 1954, he worked briefly as research director at BioRad Laboratories before becoming a senior research chemist at Dow Chemical Company, where he synthesized the first biodegradable insecticide, Zectran.

Because Shulgin made Dow a sizeable profit, he was granted the freedom to create and patent new drugs. He chose psychedelics. In the late 1950s, Shulgin experimented with mescaline, which he wrote revealed “that our entire universe is contained in the mind and spirit.” But his interest in pharmacology was sparked years earlier. While in the Navy as a teenager, he got a shot of morphine for an injury, making him wonder how drugs altered consciousness. This passion for understanding the human mind and how to unlock its potential—chemically, of course—would mark his career.

In 1966, Shulgin left Dow Chemical to freelance as a consultant and for the following decades worked from his backyard lab in Berkeley, California. In 1976, he heard about MDMA, which was first synthesized at Merck in 1912 as an unimportant precursor in a new synthesis for haemostatic substances and subsequently shelved. He went on to synthesize it, and discovered it was a powerful empathogen, “with emotional and sensual overtones.” He then introduced it to a therapist friend and word spread quickly both inside and outside the therapeutic community. Without MDMA, the dance music scene of the last 30 years would have looked entirely different.

Shulgin was a fixture in the psychedelic subculture that believed in better living through chemistry. He contributed a rational, scientific perspective to the field, coupled with enthusiasm for thorough self-experimentation.

When interviewed about the abuse potential of MDMA, which became a scheduled drug in 1985, Shulgin was quoted as saying it was “as real as the abuse potential of anything that gives pleasure and satisfaction. This applies to MDMA as much as it does to skydiving, mountain climbing and skiing.”

Shulgin died of several health complications after years of poor health, and had recently been diagnosed with terminal liver cancer. He was 88. His wife, Ann Shulgin, with whom he shared thousands of psychedelic experiences, survives him.

30 April - Q&A with Rick Strassman

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