Old Drugs, New Tricks? Psychedelic drugs as therapeutic agents

Brian Bingham
Oct 18, 2014

For as long as we have recorded history, humans have been using chemicals to alter their perception of reality. Initial experimentation likely began with naturally occurring hallucinogens found in wild mushrooms and cactuses, but soon expanded to alcohol (fermented grains), opiates (poppy seeds), and stimulants (tobacco, coca leaves) with the advent of horticulture. The chemicals found in these plants could dull pain, create a euphoric state, reduce anxiety, increase arousal, and induce a sensation of connection with the universe. These plant-based drugs rapidly became important components of human social, religious, and medicinal practices.

As scientific discovery exploded in the 20th century, our ability to refine, manipulate, and synthesize new chemicals with even stronger psychoactive properties increased. Compounds like LSD and MDMA (ecstasy) were marketed as new treatments for disorders like alcoholism, depression, and anxiety. Psychiatrists would administer these compounds during therapy sessions to increase treatment efficacy. However, in response to the dangers of recreational use and their prevalence in the counter-cultural social movements of the 1960’s and 70’s, these drugs were quickly criminalized. Consequently, support for further clinical research into their potential medicinal benefits virtually disappeared.

Recently, privately funded organizations have helped to spur new life into these research efforts. Organizations like the Multidisciplinary Association for Psychedelic Studies have advocated for and funded clinical trials to investigate the effects of MDMA on improving therapy outcomes for patients suffering from treatment resistant Post-Traumatic Stress Disorder (PTSD). In one recent study, 10 of 12 patients who received MDMA in concert with psychotherapy had a decrease in PTSD symptoms, compared to only 2 of 8 patients who received placebo. Similarly, the Hefftner Research Institute recently reported that 12 of 15 (80%) patients who took doses of psilocybin (the active ingredient in hallucinogenic mushrooms) as part of a smoking cessation therapy remained abstinent at 6 months. This is impressive because most other smoking cessation therapies are, at most, 35% effective. Even the US government has begun to investigate controlled substances as mental health treatments. NIMH-funded clinical trials of ketamine (Special K) have demonstrated rapid (<2hr post-infusion) antidepressant efficacy that can last up to a week. In addition, NIMH is currently recruiting for a clinical trial to determine if ketamine can serve as a rapid-acting treatment for suicide ideation.

These studies beg the question: how are psychedelic drugs able to have such potentially dramatic effects in the clinic but not on the street?

The answer likely lies in the interplay between a class of neurotransmitters called monoamines (serotonin, dopamine, and norepinephrine) and the brain regions responsible for emotional memories. When recalled, memories can become moldable and subject to change. Monoamine neurotransmitters are an important part of emotional processing and help modulate and consolidate emotional memories. Importantly, most psychedelic drugs elevate monoamine stimulation far beyond levels achieved naturally. Therefore, drug-induced monoamine stimulation in a safe, clinical environment may allow the patient to ascribe new emotional context to a memory during guided therapy. Presumably, PTSD patients could employ this therapy to decrease fear and anxiety triggered by reminders of past events, or substance abusers could reduce cue-induced cravings.

Unfortunately, the stigma created by criminalization has impaired the ability of clinical researchers to fully investigate psychedelic drug therapies as potential adjuvant treatments. The present studies show impressive therapeutic effects but are hampered by small sample sizes and inadequate control groups. While there are legitimate concerns about the use of psychedelic drugs as therapies, without support for responsible research, it will be impossible to resolve those concerns. Perhaps now is the time to open regulation in a way that will provide the funding and access necessary to investigate these potentially life-changing therapies.

Image: "Garish (509162157)" by aussiegall

Brian Bingham

Brian Bingham is a Neuropharmacologist with interest in the consequences of traumatic stress exposure early in life, including prenatal, infancy, and adolescence time periods. Prior to serving as an S&T Policy Fellow, he was a postdoctoral fellow at the UT Health Science Center in San Antonio where he also served as founder and president of the UTHSCSA Postdoctoral Association. In his spare time he enjoys mountain biking, horseback riding, and cooking.


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Comments (3)

Dana Allison (not verified)
October 20, 2014 at 11:15 pm
Really interesting overview on history and recent use and study of psychedelic drugs in treating specific types of mental illness. You asked a question mid-post that, from reading, I wouldn't have seen the interplay you pointed to, as the answer to why street-use of drugs do not have as dramatic effect as clinical use of the same drugs. It seems to me that in each of the studies with their reported effects of clinical use of these drugs, the therapy also included a) controlled dosing and b) psychotherapy. Perhaps this combination could also explain the dramatic differences in outcomes and would strengthen the argument for clinical trials using these drugs, under these clinical conditions.
Brian Bingham (not verified)
January 13, 2017 at 2:20 pm
Sorry I didn't make that point more clear. It definitely seems that there therapeutic efficacy is dependent on having a purposeful, guided therapy session that accompanies the psychedelic experience. It would be interesting to demonstrate this empirically by designing well-powered studies that tease apart the relative contribution of psychotherapy vs drug vs combination treatment.
Carolyn La Jeunesse (not verified)
October 31, 2014 at 8:21 pm
So glad this topic is being handled so thoughtfully. LSD in particular showed great promise as an approach to improving psychoemotional and perhaps physical quality of life for the terminally ill. Criminalization removed it from the available pharmaceutical options. I hope that with this renewed attention, LSD and other "psychadelics" can be further studied to assess their value and potential inclusion as options to improve quality of life at the the end-of-life.

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