Psychedelics

Figure 1. A 2014 study in the Journal of the Royal Society Interface. The image on the left is of a human brain on a placebo, and the image on the right is of a brain on a psychedelic.

Psychedelics are medicinal compounds which affect the functioning of the human mind. Although historically psychedelics have been held in high regard, since the 1970's they have been shrouded in taboo. This was, in part, due to a US led criminalisation effort linked to preventing a decrease in conscription for the Vietnam War. However, since the advent of The Psychedelic Renaissance this fabrication is slowly dissipating. In the scientific community, psychedelics seen as neither good nor bad, but merely tools which have the unique property of inducing neuroplastic states.

During the psychedelic experience as shown in the brain scan to the right (Figure 1) subconscious inputs open up to the conscious mind effectively allowing the user to see the delusions and fallacies under the hood. Several peer reviewed studies have now shown that psychedelic use can lead to pronounced ecological concern

Psychedelic Compounds

Figure 2. The “Classical” Psychedelics are mescaline, LSD, psilocybin, and DMT. Plus the deliriants and dissociatives.

There are 5 classes of psychedelics based upon their effect and chemistry.

Tryptamines

• Psilocybin / psilocin found in magic mushrooms.
• DMT found in acacias and ayahuasca.
• 5-MeO-DMT found in toad venom.

Ergoline

• LSD derived from the rye fungus, ergot.

Phenylethylamines

• Mescaline found in the peyote cactus an Native American entheogen.
• MDMA and 2C-B synthetic compounds made by the chemist Alexander Shulgin.

Deliriants

• Muscimol found in the toadstool, amanita muscaria.
• Ibogaine, an African entheogen.

Dissociatives

• Ketamine a synthetic anaesthesia, which globally, is the most prescribed drug in this class.

Usage

Figure 3. Economist June 2019, relative harm of different drugs.

Psychedelics are not without potential harm, however relative to alcohol and the majority of other drugs (See Figure 3) the risk is minimal. In a clinical sense, under specific priming and setting there is abundant evidence for the safety and efficacy for their use in the treatment of:

• Cyclical thought patterns:
  • Depression - multiple meta analyses results suggest that psychedelic-assisted therapy is effective with minimal adverse effects, relative to a comparable meta analysis of the effects of 21 traditional antidepressant drugs, relative to other treatments psychedelics lack the majority of serious adverse effects.
  • Obsessive compulsive disorder (OCD)
• Cyclical behavioural patterns:
  • Alcoholism - the founder of AA cured his alcoholism using LSD.
  • Tobacco Use - small study has shown an 80% cessation rate after 6 months which compare to the industry standard of 35%.
• Ecological crisis denialism - there is a lot of data to suggest that the interconnectedness felt during the psychedelic experience can lead to pronounced ecological concern.

Numerous studies and a systematic review have concluded that guided psychedelic therapy can augment the above therapeutic effects.

Mechanism of Action

Psychedelics are exogenous neurotransmitters, that cause neuroplastic, pivotal mental states. It is thought psychedelics mediate this effect by altering Brain-Derived Neurotrophic Factor (BDNF)

Psychedelic Comparison

Whilst the pharmaceutical industry markets that psychedelics can cure everything from obesity to hair loss, in reality there is little evidence that they can treat any other conditions apart from specific mental health issues. In this regard, the most commonly used psychedelics, Psilocybin, DMT and LSD have a very similar effect whilst dissociatives are more Out of Body Experience orientated. Popular opinion suggests that each psychedelic irrelevant of class has an individual nuanced effect, this can be seen by the thousands of subjective reports scattered on the internet https://erowid.org/experiences/). However, a recent analysis of 2947 publicly available trip reports concluded:

"MDMA experience reports featured an emotionally intensifying profile accompanied by many cognitive process words and dynamic-personal language. In contrast, Ayahuasca and DMT experience reports involved relatively little emotional language, few cognitive process words, increased analytical thinking-associated language, and the most semantic similarity with psychedelic and mystical experience descriptions. LSD, psilocybin mushroom, and ketamine reports showed only small differences on the emotion-, analytical thinking-, psychedelic, and mystical experience-related language outcomes. Further research has concluded: “Both doses of LSD and the high dose of psilocybin produced qualitatively and quantitatively very similar subjective effects, indicating that alterations of mind that are induced by LSD and psilocybin do not differ beyond the effect duration”.

For psilocybin, ketamine, mescaline and LSD it has been found that the psychedelic experience have yielded magnetoencephalographic (MEG) signals values exceeding those of normal waking consciousness. Indicating psychedelic drugs induce ‘heightened state of consciousness‘. The scans found the most notable effects in parts of the brain that are known to be important for perceptions, rather than other roles such as language and movement.

Medicinal Chemistry

All psychedelics are chemically unique and but can be catergorised into four main main types (see figure 2). There are three main families of chemical compounds: tryptamines, phenethylamines, or lysergamides and many tend to act via serotonin 2A receptor agonism which plays a key role in regulation of cortical function. Serotonin antagonism has been proposed as the mechanism for the subjective and biological effects of classical psychedelics as these effects are blocked after administering 5HT2AR antagonists such as ketanserin.

Side effects

Mescaline causes stomach cramps.

Duration of psychedelic state

• DMT: 30 minutes.
• Psilocybin: 3-6 hours.
• Ayahuasca 4-7 hours.
• LSD 6-11 hours.
• Mescaline: 8-15 hours.

Long lasting effect

Emotions and brain function are altered up to one month after a single high dose of psilocybin.

Psychedelic Contraindications

There are a few medicines and category of people which exclude patients from taking psychedelics:

• There is a theoretical interaction between SSRIs and psychedelics.
• There is some evidence to suggest olanzapine (an atypical antipsychotic) can terminate a trip.
• Kentanserin a research chemical and antagonist of 5-HT2A binds to the main psychedelic receptor but does not activate it. A recent study showed that giving participants kentanserin 1 hour after giving them LSD reduced the duration of LSD's subjective effects from around 8.5 hours to 3.5 hours. In theory, kentanserin might have use for reducing or terminating a psychedelic experience.
• Presence or history of psychosis;
• Presence or history of mania or bipolar disorder;

Microdosing

Figure 4. Psychedelics exert their effect experientially

The medical definition of microdosing is a dose given which is sub therapeutic, i.e. it is the dose doctors recognise as having no discernible effect. However, many claim, mainly via online survey studies, that very low doses of LSD, taken at 3–4-day intervals, improve mood and cognitive function.

In controlled studies, which in mental health are the gold standard, (see critical appraisal) the placebo effect is excluded. In all of these studies microdosing has been shown to have no effect and even in some have shown negative effects such as neuroticism. It has been suggested that this is because the experience of the trip is more important than the underlying chemical-electrical mechanisms (see Figure 3) . By propagating the myth that microdosing does have an effect this may cause people from not accessing the correct dose and getting the actual benefit from the medicine.

Oneirogen

An oneirogen, is a substance or experience which enhances dream states, in effect this could be likened to an unconscious psychedelic states.

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