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 that given the correct priming (set) and setting have potent anxiolytic, antidepressant and anti addictive effects. In some countries, they are classified as illegal, however, with the advent of the psychedelic renaissance the taboo is lifting leading to countries decriminalising and many patients gaining access via medical tourism.

During the psychedelic experience, as shown in the illustrated brain scan to the right (Figure 1) parts of the brain which do not usually communicate with one another start talking, and subconscious inputs open up to the conscious mind. The experience is thought to open a neuroplastic window giving users an opportunity to correct ruminating thought patterns thought to be the basis of mental illnesses such as bipolarity, depression, anxiety.

History

Psychedelics have been used by human civilisations for over 3,000 years. Only recently, in the 1970s, have they been mired in taboo. Currently, there is a resurgence of interest in the medicines termed the The Psychedelic Renaissance which is showing that in fact, they are one of the safest, most effective compounds for the treatment of various mental health conditions.

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 on 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 a Native American entheogen.
• MDMA and 2C-B synthetic compounds made by the chemist Alexander Shulgin.

Deliriants

• Muscimol found in 🍄 - amanita muscaria.
• Ibogaine, an African entheogen.

Dissociatives

• Ketamine a synthetic anaesthesia, which globally, is the most prescribed drug in this class.
• Nitrous oxide can induce mind-altering experiences, including feelings of bliss, spirituality, and the feeling of being outside of one's body.

Effect

Psychedelics induce a psychedelic experiences which encompass a wide range of sensory distortions, most common include:

Visual

• Diffraction
• Increased apophenia
• Object activation
• Visual acuity enhancement
• Visual agnosia
• Visual exposure to inner mechanics of consciousness

Cognitive

Novel

• Time distortion
• Conceptual thinking
• Thought loops
• Depersonalization

Enhancements

• Creativity enhancement
• Increased suggestibility
• Novelty enhancement

Suppressions

• Addiction suppression
• Personal bias suppression

Usage

Figure 3. Relative harm of drugs.

Like all medicines, psychedelics are not without potential harm. However, relative to all other drugs (See Figure 3) risk associated with their use 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%.
  • Hyper-Consumerism - several peer-reviewed studies have shown that psychedelics also work as ecodelics, medicines which can induce ecological concern.

Emotions and brain function are altered up to one month after a single high dose of psilocybin. Psychedelic use correlates to lifetimes without depression. Numerous studies and a systematic review have concluded that guided psychedelic therapy can further improve the above therapeutic effects.

Mechanism of Action

Psychedelics induce neuroplastic, pivotal mental states. It is thought psychedelics mediate this effect by altering the Brain-Derived Neurotrophic Factor (BDNF) receptor TrkB.

Psychedelic Comparison

The most commonly used psychedelics, Psilocybin, DMT and LSD have a very similar effect whilst dissociative psychedelics like ketamine have a more of an Out of Body Experience effect. This is backed up by recent, real world evidence analysis of 2947 publicly available, erowid.org trip reports which 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”.

Class	Drug	Light High Dose	Normal Dose	Maximum Safe dose	Time to Onset*	Duration of Experience	Duration of Open State
Classic	LSD	20-50 μg	150 μg	1000-3000 μg	0.25-2 hours	6-11 hours	3 weeks
	DMT	5-10 mg	40 mg	100 mg	Immediate	15-30 minutes	-
	Psilocin	5-10 mg	35 mg	150 mg	0.5 hours	3-6 hours	2 weeks
	Mescaline	50-200 mg	400 mg	1000 mg		8-15 hours	-
	Ibogaine						>4 weeks
Empathogen	MDMA	45-75mg	75-140mg		20-30min	2-4 hours	2 weeks
	2-CB
Dissociative	Ketamine						2 days
	Dextromethorphan

Figure 4. Psychedelics differ in how long they induce a social reward learning period

Dosage information frequently changes and is dependent on weight and prior medical condition. Before administering check all information with a suitably qualified professional.

A key effect of psychedelics is their ability to open a period of neuroplasticity where old habits can be erased and new habits formed. This period has been found to differ substantially between the various compounds (see Figure 4).

Medicinal Chemistry

All psychedelics are chemically unique and can be categorised into four 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 the 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.

Who would be eligible for psychedelics from a doctor?

Exclusions Criteria

Psychedelic therapy is not for everyone. There is a category of patients that have specific conditions or are taking specific medicines that should be excluded from psychedelic therapy:

• People taking SSRIs: citalopram (Cipramil), dapoxetine (Priligy), escitalopram (Cipralex), fluoxetine (Prozac or Oxactin) may experience serotonin syndrome, this is more pronounced in those taking MDMA;
• People taking olanzapine (an atypical antipsychotic) as there is some evidence to suggest it can terminate a trip;
• Presence of high degrees of Psychedelic Anxiety Syndrome;
• Presence or history of psychosis;
• Presence or history of mania or bipolar disorder;

Inclusion Criteria

To be able to obtain a psychedelic from a doctor all of the following criteria must be met:

• Over 25, this age is not written in stone and there will be some variability, however, it is thought that psychedelics should not be taken until brain growth is completed which occurs around the mid 20's.
• Diagnosed as having Treatment Resistant Depression, i.e. no adequate response to a course of appropriate antidepressant medication within a certain time.

Adverse effects

Like all medicines, without proper guidance, adverse effects can occur. As shown in Figure 3, relative to other popular medicines psychedelics cause much less harm. However, there have been some idiosyncratic adverse psychedelic effects.

Microdosing

Figure 5. 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 5) . By propagating the myth that microdosing does have an effect may cause people from not accessing the correct dose and getting the actual benefit from the medicine.

Oneirogens

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

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References