The use of psychedelics in treating disorders continues to grow and gain acceptance. Microdosing has become more commonplace, and the field of psychedelic research is back on track after a moratorium that lasted several decades. Let’s take a look at the state of psychedelic research, whether microdosing has any effects on the body, and the future of psychedelic research.
History of psychedelic research
Both neuroscience and psychiatry were interested in psychedelics during the 40s, 50s, and 60s. Research had been conducted on mescaline, the active compound in the peyote cactus early in the 20th century. However, research began in earnest after the discovery of LSD in the 40s.
The extreme potency of LSD was of particular interest. In addition, its structure is similar to serotonin, which scientists were just discovering its presence in the brain. These early discoveries reinforced the understanding of the brain as an electro-chemical messaging organ and helped solidify the discipline of neuroscience.
The psychiatry field looked at LSD as a therapeutic agent to treat psychiatric disorders. It had a powerful effect on the brain, which resembled psychosis that occurs in schizophrenia. Early research from Canada in the 1950s recognized that alcoholics frequently made improvements after reaching “rock bottom” and developing delirium tremens (the shakes) during alcohol withdrawal. Unfortunately, these addicts often died as a result of delirium tremens, so inducing the condition was clearly not an option as a treatment.
However, the researchers, Abram Hoffer and Humphry Osmond, asked if they could give a drug that is relatively safe at the physiological level that also mimics the extreme dysphoria and psychotic-like features of delirium tremens?
They investigated this idea with LSD. Their participants did not have aversive reactions that the scientists expected. Rather, they had transcendental, positive, and insightful experiences. They quickly realized that the positive experiences were more likely when they psychologically prepared participants for the drug experience, provided personal support during sessions, had participants wear eyeshades to direct their attention inward, and played evocative music to support the experience.
The new “psychedelics therapy” method was born. It is this method that is used in virtually all modern research investigating the potential therapeutic effects of high dose psychedelics. In this early era of research, promising findings were reported for a number of disorders, most notably treating alcoholism and alleviating distress in terminal cancer patients.
Recreational Use and Continuing Study of Psychedelics
Psychedelic research enjoyed significant gains after LSD became popular as a recreational drug used by the counterculture of the late 60s and early 70s. Still, some people died from overdoses. Most scientists were aware of the risks and conducted their research carefully. Many of them expressed concern over the number of provocative researchers who encourage a more reckless approach and wider use. These factors helped limit the human research that was conducted for about 25 years.
Research was allowed only under strict parameters after the drugs were made illegal. Still, a consensus developed that the drugs were too dangerous to study even under strict controls. Beginning in the mid- to late-1990s, a small number of researchers around the world, such as Franz Vollenweider, started administering classic psychedelics once again to humans.
Psychedelics such as LSD, mescaline, psilocybin, and DMT have a primary psychoactive effect mediated by a specific serotonin receptor, 5-HT2A. Most current research into these psychedelics has used psilocybin, which has a shorter duration than LSD. In addition, LSD continues to have a stigma left over from the 1960s.
Why was there such a lengthy break into psychedelic research? A key factor is that some time has passed since the 1960s. Now, the general public sees that psychedelics may indeed have beneficial effects in certain circumstances. Paradigm shifts in science can take decades to occur, and then more time passes before the mainstream public accepts the change.
Modern psychedelic research
Since the 1990s, human research using psychedelics has investigated several issues including the effects on cognition, the brain mechanisms of psychedelics, the subjective experiences that occur, and treatment of certain psychiatric disorders.
The most advanced therapeutic findings are with cancer-related distress like anxiety and depression in patients with terminal cancer.
Three randomized, double-blind studies found significant reductions in anxiety and depression. The two studies that used the largest doses found immediate and substantial decreases in depression and anxiety that persisted for at least 6 months. In one study of 51 cancer patients, 80% of patients showed substantial decreases in depression and anxiety 6 months after the treatment with only one single high dose of psilocybin.
Other studies suggest that several psychiatric disorders may show improvement through psychedelic therapy. Early non-randomized research with non-cancer patients with major depressive disorder also shows substantial improvements in depression.
Some studies have been conducted to treat tobacco addiction. The findings suggested that 3 psilocybin sessions followed by cognitive behavioral therapy resulted in significant abstinence from smoking cigarettes: 80% smoke-free at 6 months, and 60% smoke-free at an average of 2.5 years.
Some researchers have reported very early promising findings for the treatment of cocaine addiction and beneficial effects across various disorders. These are disorders that are associated with a substantial risk of death and are substantially underserved by current treatment options. More research is necessary, but the early results are very promising.
Is microdosing effective?
With psychedelics, microdosing means taking a dose of the substance so small that it does not have overt psychedelic effects. However, the amount does have discernable psychoactive effects. A microdose of LSD would be around 10 micrograms, which is an amount that brings a person just to the beginning point of a psychedelic experience.
The potential benefits range from improved athletic performance, cognitive function, and anti-depressant effects. However, there is some evidence that a placebo effect may explain some of the benefits.
Only a few articles published in the clinical literature have investigated microdosing under conditions that can control for the placebo effect. None discovered benefits. Some studies relied on surveys. While these results are valuable for documenting user claims, they are not convincing of efficacy. Results of the little double-blind research that has been conducted range from no change, to negative effects (impaired ability to accurately judge time), to increases in abuse-liability related subjective effects. In other words, participants felt just a little “high.”
These studies assessed the direct effects of microdoses after administering the drug and have not been conducted in the context of an ongoing pattern of taking the drug once every few days, which is a common method of microdosing. Thus, the studies cannot be performed in a scientific way to pinpoint beneficial effects.
It may be that a certain amount of hype surrounds the claims of benefits from microdosing. Some people are seeking an experience of “being in the zone,” a positive, confident flow to life. Many times, that can be produced by a change of actions such as smiling at strangers, taking a first step forward, or checking off the to-do list. Thus, it may be fairly straightforward to produce a placebo effect, which makes objective scientific studies more problematic.
Still, many scientists researching psychedelics believe that there is a direct pharmacological effect. The most promising area for microdosing appears to be for its antidepressant effects. It is plausible that there is some effect there. Traditional antidepressant effects going back to the 1950s have involved augmenting the serotonin system in one way or another. Thus, altering the 5-HT2A serotonin receptor over the long-term could lead to antidepressant effects.
The potential cognitive benefits should also be researched further. There are many cognitive enhancers that can provide cognitive benefit with the right context, dose, and frequency, such as nicotine, caffeine, modafinil, and amphetamines.
One concern is that those taking these drugs typically build up a tolerance and need to take higher doses. The concern is that one might become tolerant to the effects of microdosing psychedelics, although the microdosing method may minimize that risk.
All of the major classical psychedelics, including LSD and psilocybin, have effects at the 5-HT2B receptor in addition to their effects at the 5-HT2A receptor. Even the non-classic psychedelic MDMA has 5-HT2B effects. Drugs that interact with 5-HT2B are well known to lead to valvular heart disease with chronic use. This is why fenfluramine, part of the combination medication “fen-phen,” was pulled from the market. It is not likely that current treatment models with high dose psychedelics are a concern, but taking these agents chronically every few days for months or years may be a concern for heart valve disease.
Safety first
If you are considering using psychedelics, it is important to become educated on the risks.
One analysis regarding the risks of psilocybin looked at applying the factors used by the FDA to determine the scheduling of a medication. This review concluded that if psilocybin is eventually approved as a medicine, it should likely be placed in Schedule IV. It is currently in Schedule I, a more restrictive category than even cocaine and methamphetamine. Even though many sleeping drugs are in Schedule IV, there would likely be additional restrictions imposed by the FDA, such as the requirement only to administer psilocybin in the clinic with safety mechanisms in place.
These are the most relevant risks of psilocybin and other classic psychedelics. First, individuals with psychotic disorders such as schizophrenia should not take these drugs as they might trigger or worsen the psychotic process. At a sufficiently high dose, these drugs can cause overwhelming psychological effects that can sometimes lead to strong anxiety, fear, and panic. This can happen even to psychologically healthy people. The risk of a “bad trip” exists.
Supervision is absolutely necessary. In an unsupervised environment, sometimes individuals experience harm or die when they panic or make a poor decision during such experiences. It is relatively rare. But, most people don’t want to take that risk.
These drugs also raise pulse and blood pressure, so they can be a risk for those with more severe cardiac disease. Individuals in this category are at risk when doing any number of things with a moderate cardiovascular load, such as intense exercise, climbing stairs, shoveling snow, or having sex. Some research shows that headaches are more likely for about a day after using psilocybin, although they are typically mild to moderate in severity and nothing that should preclude clinical use.
One rare side effect is persistent perceptual problems, similar to the psychiatric condition called hallucinogen persisting perceptual disorder. This seems exclusively related to the recreational use of psychedelics and has never been seen in thousands of clinical research participants. This means it could be due to a very rare susceptibility or the result of any number of factors such as mixing drugs and/or alcohol.
The final risk is addiction to classic psychedelics that do not appear to lead to addiction. Rather than the clinical definition of addiction, it could become compulsive drug seeking or abuse of the psychedelic. This may be driving while using or patterns of use that interfere with your job or family relationships.
Final thoughts
The use of psychedelics for the treatment of depression, PTSD, addiction, and more is gaining acceptance and offers hope to those suffering from the conditions. We will likely see significant advancements in these areas including FDA approval of psychedelic medications for several disorders.
Academic research will continue to expand. And NIH funding for therapeutic research with psychedelics may finally resume.
Tens of millions of people worldwide suffer from post-traumatic stress disorder (PTSD). Millions more have suffered from emotional and physical abuse but never get diagnosed. On top of that, PTSD is notoriously difficult to treat and cure. Now, MDMA-assisted psychotherapy is garnering some interest. Early research has produced some amazing results.
In MAPS’ completed phase 2 trials with 107 participants, 56% no longer qualified for PTSD after treatment with MDMA-assisted psychotherapy, measured two months following treatment. At the 12-month follow-up, 68% no longer had PTSD. Most subjects received just 2–3 sessions of MDMA-assisted psychotherapy. All participants had chronic, treatment-resistant PTSD and had suffered from PTSD for an average of 17.8 years. On August 16, 2017, the FDA granted Breakthrough Therapy Designation to MDMA for the treatment of PTSD.
If MDMA is successful as a legal treatment for PTSD, it will set precedent and lead to research into many other psychedelic compounds for many conditions.