Psychedelics as Nootropics?

The use of classical psychedelic substances for therapeutic purposes has surged in recent years. Although in its infancy, research has also alluded to the potential benefits of "microdosing" psychedelics for health and wellness, namely by lowering depression, anxiety, and stress as well as enhancing cognitive performance [2].

Today’s article poses the following questions: is it possible for psychedelics to be nootropics? If so, how? And could the neural plasticity-altering effects of these well-known drugs be harnessed to enhance brain function (i.e., are they psychoplastogens)? 

But first... what are nootropics again? 

Nootropics, Revisited

Before we dive deep into LSD, psilocybin, DMT, MDMA, and ketamine, here’s a quick refresher on nootropics. 

The “normal” (i.e., old) definition of nootropics is as follows: a drug, supplement, or other compound that is associated with improvements in aspects of cognitive function, such as memory, attention, executive function, vigilance, creativity, and/or motivation. They are often called "smart drugs" or "cognitive enhancers," and include a broad range of compounds, such as stimulants, that can act on neurotransmitters in the brain and throughout the body [1].

The Troscriptions definition (i.e., the new and improved definition) of nootropics both broadens this definition and enhances it with three major categories: Health Optimization Nootropics (HONs), Performance Optimization Nootropics (PONs) and Bluetropics. We have blog articles on both HONs and PONs with one on Bluetropics soon to follow. 

The key with these new categories is that any substance that enhances brain function may very well be a nootropic... whether it’s healthy for the brain (HON), making the brain perform better at a task (PON), or both (Bluetropic).

Let’s see how psychedelics fit in! 

The Historical Use of Psychedelics and their Application in Research 

Since antiquity, humans have used psychedelics in rituals and as medicine [3]. Perhaps you’ve heard of lysergic acid diethylamide (LSD or "acid"), psilocybin ("magic mushrooms"), and dimethyltryptamine (DMT, the "spirit molecule"). These all act as serotonergic agonists. This means that they act in a similar manner to serotonin itself, a neurotransmitter responsible for modulating behavior, mood, reward, cognition, learning, memory, and many other physiological processes [4].

Modern psychedelic research arose in 1938 when Albert Hofmann synthesized LSD and five years later became the first person to ingest it. This ushered in a burgeoning period of scientific and cultural experimentation in the 1950s and 1960s, that was then ground to a halt in the 1970s and 1980s by government interventions against the "hippie" counterculture movement [5]. The U.S. government reclassified psychedelics as Schedule 1 drugs in 1970, ultimately ending research on these substances for decades [6]. 

Times are a changing now, though, as studies are taking place in research institutions and private practice settings that seek to enhance our neuroscientific understanding of how psychedelics impact the nervous system, in addition to their potential uses in health and disease [5].

In short, there is mounting evidence that many of these compounds are not just psychedelics (mind altering), but also nootropics and psychoplastogens. This latter term refers to compounds that produce rapid and sustained effects on neuronal structure and function, intended to manifest therapeutic benefits after a single administration. 

The Nootropic Effects of Psychedelic Substances 

LSD 

Lysergic acid diethylamide (LSD or "acid") is a classic drug that is well-known in the public consciousness for its psychedelic properties.

Recent research from Brazil has shown that in rodents and human brain organoids (essentially brain tissue grown from stem cells), LSD has nootropic effects. These include enhancing neural plasticity, improving visuo-spatial memory, and supporting cognitive function [7].

It is thought that the improved neural plasticity (i.e., the driving force for cognitive gains) is caused by the upregulation of dendritic spines, increased dendritic complexity, increased synthesis of synaptic proteins, and increased synaptic responses [8]. This is particularly important because the loss of dendritic spines is a central feature of depression and other neuropsychiatric disorders [9].

Dendritic spines are a reservoir for synaptic strength and serve to increase the number of possible contact points between neurons [10]. Rodent studies have shown that LSD treatment nearly doubled the number of dendritic spines per unit length, while also favoring a shift towards a more "youthful" dendritic spine type and increased synaptic density [8]. Memory storage is believed to be highly dependent on synaptic changes of this kind – synapses being the specialized sites of cell to cell contact that connect nerve cells within the overall central nervous system [11].

Psilocybin 

Psilocybin is the active chemical found in so-called "magic mushrooms" and is the most commonly used psychedelic (~85% of the study sample) when microdosing, according to recent research [2].

Rodent studies have shown that low doses of psilocybin tend to favor increased neurogenesis and also extinguish the classically-conditioned fear response, pointing to the use of this psychedelic against post-traumatic stress disorder, for example [12]. 

In patients with major depressive disorder, psilocybin therapy increased cognitive flexibility for four weeks following treatment [13]. A separate study looked at the administration of a single high dose of psilocybin (25 mg), revealing that positive affect was still elevated one month after dosing, whereas trait anxiety was reduced [14]. The authors proposed that negative affect might be a potential therapeutic target for psilocybin treatment. 

DMT 

Dimethyltryptamine (DHT), most famously found in ayahuasca, the psychoactive brew used for ceremonial and social purposes by the indigenous peoples of the Amazon basin, is rapidly gaining focus in Western nations.

As with the previous two psychedelics, much of the evidence is from rodent studies, but nevertheless DMT has been shown to increase neurogenesis (the formation of new neurons in the brain), leading to the proliferation of neural progenitor cells [15]. A very interesting aspect of this study is the fact that the treated mice performed better in memory function tests when compared with controls, suggesting an ability of DMT to enhance spatial learning and memory tasks [15].

In a similar manner to LSD, DMT treatment also brings about an increase in dendritic spine density [8], which can help offset depression and anxiety while improving cognitive performance.

Ketamine 

Ketamine is another old drug (it was first synthesized in 1962) that has been used as an anesthetic in animals and humans. 

At low concentrations (much lower than those needed to bring about anesthesia), ketamine offers promise for addressing treatment-resistant depression. This effect is likely due to ketamine’s action on a protein called brain-derived neurotrophic factor (BDNF) in the hippocampus [16]. 

The subacute and long-term dosing of ketamine on a daily basis has also been shown to reverse the cognitive dysfunction caused by chronic mild stress, while also offering antidepressant and anxiolytic (anxiety-reducing) effects [17].

Although these studies were carried out in rats, they show the potential therapeutic value of ketamine microdosing to enhance cognitive health.

MDMA 

Ecstasy or 3,4-methylenedioxymethamphetamine (MDMA for short) has a reputation as a recreational drug among young people, but emerging research has explored its effects on post-traumatic stress disorder, such as that seen in veterans of armed conflict. 

MDMA is another very old drug (over a century!) that acts as a central nervous system stimulant that causes altered sensations as well as enhanced energy, empathy, and pleasurable sensations.

When used in conjunction with psychotherapy, MDMA has shown some promising effects in people with PTSD, improving symptoms of depression and reducing PTSD symptoms as measured using the CAPS-IV scale [18].

Research on MDMA for other aspects of health is currently in its infancy, despite attracting considerable attention in recent years. 

Ongoing Research (and how you can support it!)

The Multidisciplinary Association for Psychedelic Studies (MAPS for short) is at the forefront of research on psychedelic compounds.

Founded in 1986, they are a non-profit research and educational organization dedicated to supporting psychedelic research, the reform of drug policy, and educational promotion on these crucial topics.

They seek to develop medical, legal, and cultural contexts to allow people to benefit from the careful use of psychedelic substances and marijuana. 

You can support their important work here.

There are also hundreds of clinical trials ongoing or soon to start in this field that can be researched at clinicaltrials.gov as well. 

Summary*

So are psychedelics nootropics? From what we’ve discussed above, the answer is very likely yes. And they are nootropics that belong in the PONs category because they stimulate the release of various neurotransmitters in supra-physiologic quantities.

A more complete term for them, however, is psychoplastogenic PONs due to the way these compounds also change the wiring of the brain with just a single or a few sessions. 

*Tro Nation, this article is for informational purposes only. All drugs mentioned in the article, aside from ketamine, are still Schedule 1 substances in the United States. However, this may change soon for MDMA, which is currently in phase III trials.

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