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What is DMT therapy?

DMT as a molecule

By Dr Carol Routledge, Chief Medical & Scientific Officer at Small Pharma

DMT-assisted therapy is a novel psychedelic therapy which aims to treat a whole suite of mental health problems that we have sadly come to take for granted as part of 21st century life. Early trials are investigating DMT-assisted therapy in the treatment of depression. The treatment consists of a patient taking a controlled dose of the psychedelic drug DMT under the supervision of a psychotherapist within a framework of traditional talking therapies. While research in this area is still in its infancy, there are early indications that DMT-assisted therapy could be of huge benefit to the millions of people worldwide who suffer from poor mental health.

What is DMT?

DMT is short for N,N Dimethyltryptamine, which is a naturally-occurring, fast-acting psychoactive molecule. It is present in a wide variety of plants and animals (including humans) and it can also be synthesised in a lab.

Chemically speaking, DMT is part of the tryptamine family of indole alkaloids. It is similar in chemical structure to serotonin – the neurotransmitter most closely associated with happiness and wellbeing, as well as sleep – and it also resembles “classic” psychedelic drugs, such as psilocybin and LSD.

Similar to these “classic” psychedelics, DMT works by binding itself to a range of receptors in the brain, notably the 5-HT2A serotonin receptor. This can have the effect of altering visual perception, interoception (the way the mind processes what is happening in the body) and the way that the person under its influence experiences reality for the duration of the drug’s effect – which typically lasts 20-30 minutes. This duration of action is significantly shorter than the psychedelic experiences induced by LSD or psilocybin, opening up new possibilities for clinical implementation.

Why is there so much scientific interest in DMT right now?

DMT has been involved in rituals and ceremonies by many cultures across the world for centuries. It is, for example, the main psychoactive compound in ayahuasca, the sacred tincture used in ceremonial rites by the indigenous Quechua people in South America.

In common with other psychedelic treatments such as LSD, psilocybin, MDMA and ketamine, DMT is now attracting serious scientific interest as a treatment for depression – which the World Health Organisation now recognises as the leading cause of disability worldwide. Clinical trials have now vouched for both the safety and efficacy of various psychedelic medicines. In the clinical trials that have been carried out so far, psychedelic medicines have appeared to be both safe and effective as treatments, giving many mental health practitioners reason to hope that they represent a paradigm shift in the way that we treat depressive disorders.

While DMT research is still in its infancy, the Phase I trials recently conducted by Small Pharma on healthy volunteers with no prior experience of psychedelic drugs have indicated that the drug is safe and well-tolerated. The research team is now conducting Phase II clinical trials in patients with moderate and severe Major Depressive Disorder in order to test its efficacy as a treatment.

What is the DMT experience actually like?

Since everyone experiences reality in a slightly different way to begin with, DMT’s particular effects are unique to each individual and often hard to put into words. However, there are common themes. Anecdotally, patients often report visual hallucinations and out-of-body experiences. It is also common for them to feel as if they are in the presence of an “entity” – perhaps personified as a “helper” or “guide”, perhaps as a more abstract feeling of benevolence or goodness. The experiences usually have a strong autobiographical component too, which can help patients to reach insights that were elusive to them before.

Research suggests that DMT’s main function is to modulate or disrupt the ingrained neural process associated with “internalising” disorders such as depression and addiction. In other words, patients who usually feel trapped within negative thought patterns can find a way out of them. This leaves them more receptive to therapy, through which they are often able to find fresh perspectives that were hard to reach by more conventional means.

What role does therapy play in the treatment?

The “therapy” part of “DMT-assisted therapy” is as important as the “DMT” component. The treatment should only be given in a controlled setting under the supervision of a specially-trained psychotherapist – who plays a crucial role before, during and after the DMT experience.

At the outset, the therapist meets with the patient, establishes a trusting relationship, prepares them for what to expect from the treatment, and helps to set their intentions. During the treatment itself – which takes place in a sympathetically-designed, comfortable environment – the therapist remains on hand as a reassuring presence. And after the treatment, the therapist discusses the experience with the patient as part of their integration therapy. The aim is to help them to interpret what they saw and felt, draw on their new insights and perspectives, and break out of negative patterns of thought and behaviour.

How do people respond to DMT?

In Phase I trials, DMT was administered to 32 healthy volunteers with no prior experience of psychedelic drugs. DMT appears to have a good safety and tolerability profile compared with other medicines.

Elsewhere within the published literature, three out of 100 participants across five different DMT trials have briefly experienced slightly raised heart-rate and blood pressure. Three further participants described the experience as “unpleasant” or “dysphoric”. However, it’s worth noting that these risks can be influenced by dosing and supporting the patient before, during and after the drug experience.

How does DMT compare with other psychedelic drugs?

Recent Phase I trials funded by Small Pharma were the first certified and regulated clinical trials into DMT for major depressive disorders (MDDs). The trials established that the drug is safe and well-tolerated, which provides a basis for further trials into the drug’s efficacy. However, it is too early for studies to compare DMT-assisted therapy to different types of psychedelic-assisted therapies.

In the absence of clinical data, however, the annual Global Drugs Survey – an anonymous annual survey of over 20,000 psychedelic drug users – provides an interesting, albeit limited, snapshot. Compared with LSD, psilocybin and ketamine; DMT was rated the drug with the highest “strength of pleasure”, the lowest “negative effects while high”, the lowest “risk of harm” and the lowest “come down after use.”

Isn’t the DMT experience rather intense?

It is true that DMT is thought to offer a more immersive experience than LSD or psilocybin – though over a much shorter period of time. A typical DMT experience lasts less than 30 minutes, while a psilocybin experience can extend over five or six hours.

People under the effect of DMT often describe a feeling of transcending one’s body; perceived communication with other “entities”; the temporary loss of one’s usual sense of self (also known as “ego-dissolution”); reflections on death, mortality and the after-life associated with near-death experiences; and feelings of love, connection and being fully in the moment”.

So, yes, all this could be described as “intense”. If the patient understands what to expect and the therapist is sensitive to their apprehensions, intensity may not necessarily be a bad thing. All psychedelic experiences have the potential to be challenging – indeed, it may well be the case that more challenging experiences that lead to more therapeutic benefits in the long term.

Is DMT the same thing as ayahuasca?

Not quite. DMT is the main psychoactive ingredient in ayahuasca but there are significant differences between taking a controlled dose of DMT within a therapeutic setting and drinking an ayahuasca brew as part of a ceremony.

Ayahuasca is made by boiling the leaves of the shrub Psychotria viridis (which contains DMT) with the stems of the vine Baniteriospsis caapi, which contain additional psychoactive properties as well compounds that stop the body from metabolising DMT as fast as it normally would. There are two main effects of this: ayahuasca is effective when taken orally (where pure DMT is not); and an ayahuasca experience lasts far, far longer than a DMT treatment. However, a typical ayahuasca experience also brings uncertainty when it comes to dosing levels, the trustworthiness of organisers and fellow participants, and the overall legality.

I’ve read about 5-Meo-DMT too, is that the same thing?

No. There has been a flurry of interest in the hallucinogen 5-Meo-DMT, which is sometimes known as “toad” as it is derived from the crystallised secretions of the Bufo Alvarius toad. It is part of the same family of tryptamines as DMT – as is psilocybin and serotonin – but it’s not the same thing.

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