Psychedelics

Psychedelics are medicinal compounds which affect the functioning of the human mind. Historically, psychedelics have been shrouded in taboo, however with 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.

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.

The human brain is the result of evolution following a long collective history of around 4 billion years. Part chemical, part electrical, it is a neurochemical machine dealing with a cacophony of signals resulting in consciousness. The brain, in fact, sits at the centre of so many inputs they were pushed out of the conscious mind into the subconscious to stop too much noise overwhelming the system.

During the psychedelic experience as shown in the brain scan above (Figure 1) some of these subconscious inputs open up to the conscious mind. Effectively allowing you to see what is under the hood. However, as we are only built to pay attention to one or two things at one time this experience is often overwhelming, leaving us vulnerable.

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

Psychedelics are tools, like a gun which is neither bad nor good, it is the intention behind their use that creates their effect. 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 - several studies have shown that psychedelic use leads to pronounce ecological concern. It has been suggested that this may be because as perceptual frameworks dissolve, the rationality of common good between humans precipitates.

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 is a theoretical interaction between SSRIs and psychedelics.

Microdosing

Figure 3. 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.

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References