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Dr Mourad Wahba talks micro- and macrodosing

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Dr Mourad Wahba is a psychiatry trainee, currently working with the Regional Affective Disorder Service in Newcastle, a tertiary service that specialises in difficult-to-treat mood disorders. Mourad has a special interest in mood disorders, substance misuse and psychedelic assisted psychotherapy. Here, Mourad explains the difference between macro- and microdosing, and shares his view on the use of psychedelics in psychiatry.


As I write this, there’s an explosion of chemicals that are being studied for their therapeutic potential, all under the umbrella term of ‘psychedelics’. In this blog, I focus on the ‘classical’ psychedelics which include substances like LSD, psilocybin, and di-methyl-tryptamine (DMT).

Psychedelics are having a moment in the spotlight, after a long period of being stigmatised and viewed mainly as drugs of abuse with significant harm potential and the spread of bizarre folk tales of people thinking they’re an orange and trying to peel themselves (I’ve actually heard this one myself). Psychedelics seem to lend themselves to extreme narratives. They’re either the ‘drugs of the devil’ that should be avoided at all costs, or a Godsend that will treat anything from panic attacks to cancer. Lately, the narrative seems to be leaning towards the latter.

The truth is, they are remarkable chemicals that interact with the brain in unique and interesting ways. They seem to have the ability to elicit immediate changes which long outlast their acute effects, such as changing long-held beliefs, persistent patterns of thinking, or even a person’s idea of who they are – which is the really exciting thing about working with them. These properties render them potentially powerful therapeutic tools to help treat disorders such as depression, addictions, and end-of-life anxiety. That being said, they are just tools, with benefits and harms, like any other. We don’t really know how they work yet, or even how to best use them! At this point, there are two main methods of use: macro- and microdosing.

Macrodosing refers to use of a medium to high dose, with the focus being on the experience that arises. Such experiences are by their very nature ‘ineffable’. People report being outside of themselves, experiencing consciousness without a ‘self’, and even meeting God, which explains why they are sometimes viewed through a ‘mystical’ or ‘spiritual’ lens. People are also often taken on inner journeys which last for hours, where they encounter anything from old memories to symbolic representations of their lives and inner worlds. This experience is believed to be at the heart of the treatment, with preparation sessions beforehand to give people an idea of what they’re about to embark on, and integration sessions afterwards to think about the experience and learn how to implement any perspectives gained into daily life.

Macrodosing is the more common method studied, and is what I’ve been focusing on here in Newcastle. In my experience, depression improved quickly and dramatically for some participants and was sustained for months, which is a recurring finding in current research trials. For others, the road was more difficult, and their experiences were challenging and at times frightening, requiring support and reassurance throughout the journey. This can be destabilising and lead to worsening symptoms, and a period of deterioration. Sometimes people work with the challenging experiences that arise and ultimately improve, but other times people can be left with difficult experiences and need longer-term support. Research in this area is lacking and more focus is needed to further understand these challenging experiences, and how best to work through them.

Microdosing, on the other hand, refers to repeated miniscule doses that are ‘sub-perceptual’, meaning that they shouldn’t have psychoactive effects. There are several regimes out there, usually involving dosing on some days and taking breaks on others e.g., dosing one day and taking two days off. The interesting thing about microdosing is that anecdotal reports and retrospective surveys of microdosers are very positive, highlighting a range of benefits including an increase in creativity, well-being, mood lift, and improvement in cognition. However, it doesn’t seem to stand the test of randomised controlled trials, which so far have concluded that the effect is subjective, influenced by expectancy and can be explained by the placebo effects. It is still early days for this to be conclusive, and contradicting evidence is already starting to appear. For example, a randomised controlled trial in March 2023, concluded ‘improved ratings of creativity, connectedness, energy, happiness, irritability, and wellness on dose days relative to non-dose days but there was no evidence of improvement on cognitive tasks. There was also a reported side effect of anxiety, which led to discontinuation for some – so the jury is still out on that one!

Despite the uncertainty around mechanisms, harms and best methods of use, what is certain is that these are powerful chemicals with a lot of potential that need to be thoroughly researched. Unfortunately, legislation and current scheduling is getting in the way of research. Psilocybin and LSD are still ‘Schedule 1’ drugs, reported to have ‘no medicinal value and a high potential for abuse’ which we now know is not true and makes little scientific sense. This makes studying these substances very hard, and treating patients with them even harder. With the new evidence emerging, now seems like a good time to re-schedule.

In my view, this renewed interest in psychedelics is incredibly promising for the future of psychiatry. These drugs offer more than just a range of potential new treatments for debilitating illnesses that are very difficult to treat. Their mechanisms also allow us to look at psychiatric illnesses and treatments through a new lens, offering new insights into the nature of the very illnesses we’re treating. I’d say in 10 years, psychiatry will look vastly different.

I can’t write about this topic without conveying gratitude to the team at Cumbria, Northumberland, Tyne and Wear Trust who worked so hard to deliver the ‘psilocybin for treatmentresistant depression’ study in Newcastle, sponsored by Compass Pathways. in Newcastle. Anna Massey, our lovely and resourceful study co-ordinator. Jill Simmons, Wendy Hall, and Linda Davison, our kind, supportive and hard-working therapists. Our diligent and experienced R&D department managing it all behind the scenes. My fellow sub-investigator Dr Caroline Hayes who single-handedly kept the long-term follow-up trial going, and of course Professor Hamish McAllister Williams, our Principal Investigator, supervisor, and mentor, without whom none of this would be possible.

To learn more about this study and other current and future studies happening in the region, please visit: Northern Centre for Mood Disorders – NCMD (mood-disorders.co.uk)

For resources on managing your mental health and finding support within the region, please visit: https://northernmentalhealth.org 



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