Tuning in

As I conclude this two-part Health Yourself series on psychedelic science, I will focus on current studies investigating the therapeutic safety and efficacy of certain drugs used in conjunction with psychotherapy. This expanding area of research is geared toward treating patients diagnosed with such neuropsychiatric disorders as depression, anxiety, substance abuse, and post-traumatic stress disorder (PTSD).

Most psychedelics act by directly affecting serotonin 2A receptors. These receptors are known to alter human consciousness as well as other biological/psychological functions, including mood, cognition, reward, learning, and memory.

Other neurotransmitters, particularly dopamine and norepinephrine, are affected differentially by specific psychedelics. Dopamine is the brain neurotransmitter that serves as a “reward center” and influencer of memory, movement, motivation, mood, sleep and arousal, lactation, and attention. Norepinephrine, or noradrenaline, is a neurotransmitter and a hormone; it plays an essential role in the body’s “fight-or-flight” response. It is important to note that each psychedelic substance displays different psychopharmacological properties and different therapeutic efficacies in different people.

Another significant area of neuropharmacology research focuses on healthy participants to help understand how psychedelics affect the nervous system.

Psychedelics as medicines

More basic research studies and clinical trials using psychedelics are underway today than at any time in history. This worldwide research explosion reveals promising therapeutic uses of psychedelics for treating mental health disorders.

Acutely, psychedelics produce perceptual distortions, psychological experiences, and altered moods. These effects may be accompanied by imaginary hallucinations. Users report a reduced sense of self-referential awareness, termed “ego dissolution.” Also, research suggests that psychedelics, particularly psilocybin (magic mushrooms), can evoke mystical-type experiences that impart personal meaning and spiritual significance. However, variations in the way individuals experience the same dose of a psychedelic depends mostly on set and setting, i.e., a person’s internal state of mind and the external environment in which the psychedelic is used.

Early research

Cary Grant began experimenting with LSD in the late 1950s, before it became more widely popular. He began using it in a therapeutic setting with his radiologist. (Image: Wikipedia.)

Historical accounts, including carvings found in South America, suggest humans have been using hallucinogenic mushrooms since before 1000 B.C.

German scientist A. Heffter was the first Western scientist to isolate the primary psychoactive alkaloid found in the peyote cactus. It was 1896, and he named the alkaloid mescal (mescaline); it was the first psychedelic compound to be isolated and identified from its natural source, making it available for laboratory synthesis. Additional small-scale studies with mescaline and other psychoactive plants took place at the turn of the century, but scientific interest in psychedelics was relatively dormant until the discovery of the first synthetic hallucinogen, LSD, in 1936.

In 1947, W.A. Stoll, M.D., working with A. Hofmann, published the first systematic investigation of LSD using healthy research subjects and schizophrenic patients at the University of Zurich. This fundamental publication provided a scientific description of all the basic features of LSD inebriation and classified LSD as a phantasticum – a drug category capable of producing hallucinatory experiences.

Catalyzed by early reports on the unique potency and remarkable subjective effects of LSD, psychologists and psychiatrists in research and clinical practice began to experiment with patients in the 1950s. It’s estimated that tens of thousands of patients were treated with ‘psychedelic psychotherapy’ during a 15-year period.

Unfortunately, most research at this time was haphazard and unregulated, resulting in mixed reports regarding LSD’s safety and efficacy. The literature reported mostly positive effects when the drug was used on carefully screened patients in a clinically appropriate environment. But once it escaped the laboratory, LSD became the counterculture’s unsupervised and recreational “drug of choice,” and Congress responded by introducing regulations.

By 1965, the government halted all production of LSD and associated research. In 1970, the Controlled Substances Act came into force, creating five drug schedules. Schedules I and II, which included all psychedelics, require(d) a special license from the FDA to possess or use in research or clinical practice.

Current investigations

More basic research studies and clinical trials using psychedelics are underway today than at any time in history. (iStock.)

More basic research studies and clinical trials using psychedelics are underway today than at any time in history. These psychedelic agents are currently under controlled scientific investigations to determine their potential benefits (and harms) as adjuncts to psychotherapy. Below I share the associated research consensus about their general effects and possible therapeutic uses and the potential liabilities related to illicit, unsupervised, or nonmedical uses.

In June 2023, the U.S. Food and Drug Administration published new guidelines for researchers investigating the use of psychedelic drugs to treat medical conditions, including psychiatric or substance use disorders. This is the first FDA draft guidance that presents fundamental considerations to the industry when designing clinical trials for psychedelic drugs.

LSD

Ergot fungus and other sources of lysergic acid amide.
General effects: Initiates serotonin response through 5-HT2A receptors, dizziness, weakness, tremors, paresthesia (burning or prickling sensation), altered consciousness (visions, auditory distortions, ideations), altered mood (happy, sad, fearful, irritable), distorted sense of space and time.
Therapeutic uses: Addiction (e.g., alcohol), anxiety associated with terminal illness.
Potential harms: Psychosis (loss of contact with reality), hallucinogen-persisting perception disorder.

Psilocybin

Magic mushrooms, various species.
General effects: Initiates serotonin response through 5-HT2A receptors, dizziness, weakness, tremors, paresthesia (burning or prickling sensation), altered consciousness (visions, auditory distortions, ideations), altered mood (happy, sad, fearful, irritable), distorted sense of space and time.
Therapeutic uses: Addiction (tobacco, alcohol), anxiety associated with terminal illness.
Potential harms: Psychosis (loss of contact with reality), hallucinogen-persisting perception disorder.

Ayahuasca brew

Admixture from the Chacruna leaf (Psychotria viridis), Chagropanga vine (Diplopterys cabrerana), Ayahuasca vine (Banisteriopsis caapi), and other assorted plants containing DMT.
General effects: Initiates serotonin response through 5-HT2A receptors, dizziness, weakness, tremors, paresthesia (burning or prickling sensation), nausea, vomiting, altered consciousness (visions, auditory distortions, ideations), altered mood (happy, sad, fearful, irritable), distorted sense of space and time.
Therapeutic uses: Addiction (alcohol, cocaine, tobacco), depression, anxiety.
Potential harms: Psychosis (loss of contact with reality), serotonin toxicity, dangerous medication interactions.

Mescaline

Peyote cactus (Lophophora williamsii); San Pedro cactus (Echinopsis pachanoi).
General effects: Initiates serotonin response through 5-HT2A receptors, dizziness, weakness, tremors, paresthesia (burning or prickling sensation), altered consciousness (visions, auditory distortions, ideations), altered mood (happy, sad, fearful, irritable), distorted sense of space and time.
Therapeutic uses: Addiction (alcohol).
Potential harms: Psychosis (loss of contact with reality).

MDMA

Sassafras tree (Sassafras albidum — Source of safrole precursor chemical).
General effects: Initiates serotonin, dopamine, and noradrenaline effects, arousal, perceptual alteration, enhanced empathy, and sociability.
Therapeutic uses: Post-traumatic stress disorder.
Potential harms: Memory impairment, sleep disruption, short-term depression, psychosis (loss of contact with reality).

Ketamine

Ketamine hydrochloride — Laboratory-produced nonbarbiturate dissociative anesthetic derived from phencyclidine in 1962.
General effects: Hallucinogenic effects, distorts perception of sight and sound, feeling of disconnectedness.
Therapeutic uses: FDA-approved medical product (in 1970) as a short-acting anesthesia and procedural sedation for treating severe pain, including trauma, fractures, abdominal and flank pain, low-back pain, and extremity pain. Recently approved for treatment-resistant depression, currently in Phase 2 clinical study to treat Parkinson’s disease and Amyotrophic Lateral Sclerosis (ALS).
Potential harms: Nausea, vomiting, dizziness, diplopia, drowsiness, amnesia, anxiety, confusion, disorientation, dysphoria, dissociative state.

Final words

It’s encouraging to see the rising interest in cutting-edge, well-controlled, and rigorous research into psychedelics as a potential aspect of psychotherapy treatment.

Most research suggests strong promise for positive outcomes regarding such neuropsychiatric disorders as depression, anxiety, substance abuse, and PTSD, especially for those who have not responded to other treatments and who hope to avoid long-term treatment via standard medicines. In addition, most psychedelics appear non-addictive with few negative side effects.

More and more world-renowned research institutions are conducting high-level, multidisciplinary research on psychedelics as medicine, both from a fundamental neuroscience understanding and a therapeutic approach. To this end, the University of Michigan Psychedelic Center (M-PsyC) stands at the forefront of some of these advances.
 
 
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