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Microdosing: separating fact from fiction

Experts discussed microdosing at the Microdose Wonderland conference in Miami. 

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Microdosing: separating fact from fiction

A group of experts gathered to discuss microdosing and separate the fact from the fiction regarding the safety and efficacy of the practice. 

The last few years have seen a rapid emergence of people self-medicating with low amounts of psychedelic substances such as psilocybin or LSD – known as microdosing. Reports of increased productivity, and reduced anxiety and depression have been grabbing headlines, but does the evidence support this?

Discussing the benefits and the “shadow side” of microdosing at the Microdose Wonderland event, conference panel members explored the paradoxes of the practice.

The experience of microdosing

Panel host, Paul Austin, founder and CEO of Third Wave highlighted that Albert Hoffman first talked about microdosing in a High Times article in the mid-70s, noting how 25 microgrammes of LSD would be useful as an antidepressant. Austin described the practice as “something that has been a bridge between our normal waking state of consciousness and the chaos that comes from high doses of psychedelics.”

“For me, microdosing sheds a lot of anxiety, lets me be really present in conversations,” said Steven Holdt founder and CEO of Tune In Psychedelics. “So, instead of my brain running through a million things in my mind, I can actually be open and listen to people and connect with people better.”

Countering this experience, Dr Erica Zelfand, physician at Simba Health, noted: “Microdosing has helped me feel like everyone is mad at me, and like I am really nervous and want to go home and hide. So, I don’t microdose. I have experimented with it a little bit, that’s the psilocybin and then if I microdose LSD, I turned into a cyborg and get a lot of work done, and I don’t want to talk to you. 

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“That being said, I know that we are all wired a little differently and I do help my patients with microdosing, and that does different things for different people. So, I have seen the benefits that way.”

Natasha de Jong, co-founder and CEO of Earth Resonance, added: “What we have noticed is that the microdose is going help with breaking unhealthy habits – it is not from a force of willpower. I would describe it as being more from an “inner being”, a source that is giving you insights into why you are actually showing the behaviour and giving you the answers to that. 

“It gives you the insight to actually make a change and choose differently, and you can do it now. Not tomorrow, not yesterday – you live here in the now. Tthat is where microdosing helps you – to live in the present moment and to not worry about what’s tomorrow or fears for the future or worries.  I think it is also such a beautiful tool for PTSD through really integrating that.”

Limited research

Current clinical research is limited: the University of Chicago carried out a study on micorodsing LSD, and the Beckley Foundation looked at microdosing for brain-derived neurotrophic factor (BDNF), along with an experimental citizen science research study exploring the placebo effect of microdosing, and a further study has suggested psilocin (psilocybin is converted to psilocin in the gut upon ingestion) could cause cardiotoxic effects, to name a few. 

Panel member, Judy Blumstock, founder and CEO of Diamond Therapeutics, which is carrying out research on microdosing and published a paper earlier this year , said: “I think that 2021, when we look back at it, is going to be a watershed year – not just our study – but a couple of other studies.

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“They will be showing these very low dose effects in animals that I think are a watershed for us this year.”

Gregory Ferenstein, CEO at Frederick Research, added: “I think what the [placebo] study showed was that if you do psychedelics without any help, without any professional oversight or mindfulness practice, you are not going to get much out of it. And I don’t think that’s controversial.”

Calibrating dosing 

Austin highlighted the importance of calibrating microdoses due to individual differences, noting “what might work for someone is going to be totally different for another individual”. 

Dr Zelfand said: “So far as I know, there is no substance that I have found – a medicine, herbal, natural or synthetic – that works well for everybody. 

“What I have found is that the people who tend to do well with microdosing are the folks who are willing to take a more active role in their healing and who aren’t expecting the microdose to just solve all the problems for them so they can take a backseat and get better. 

“These are the folks that are wanting to maybe meditate more regularly or put their phones down at 8 pm and have less screen time and make other healthy changes in their lives. The microdosing is like a four-wheel drive for them to do that.”

The shadow side of microdosing

Although anecdotal evidence is pointing to a number of benefits from the practice, some people with certain medical conditions or psychological dispositions should not microdose, highlights Dr Zelfand.

“If we are talking about microdosing being like a kind of amplifier, we need to consider what it is that we’re amplifying. And I have seen microdosing push patients into manic states. And I’m not talking about flow states. I’m talking about true mania, and even psychosis.

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“There is still a lot that we don’t know about psychedelics. We’re learning a lot – from a research perspective is has been a bit like drinking out of a fire hydrant. We have all this information coming at us, and with microdosing, we don’t have as much data yet. So, it’s a little trickier to do studies in human subjects because these are controlled substances, and to do a microdosing study you have to send a person home with the substance, so then you’re trusting them not to divert it.”

Zenfeld notes that although for some the practice can arouse insight and creativity, in some people it can irritate the nervous system.

“In terms of folks who tend not to do well with microdosing, based on the limited literature that we have – individuals who have red green colour blindness, not always, but sometimes, they are at risk of getting “tracers”, which is when objects move, it looks like they have a trail of light after them. 

“Microdosing can also irritate people who have generalised anxiety disorder. So, not social anxiety, or situational, but low-grade anxiety – sometimes it really irritates them. As well, individuals on the autism spectrum tend to need much higher doses than what a microdose is going to give them. And then, individuals with a strong family history or personal history of mania or psychosis.”

The panel concluded by emphasising the importance of mindfulness practice when undertaking a microdosing protocol.

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Clerkenwell Health is launching a free UK psychedelic therapist training programme

In this article, communications associate at Clerkenwell Health, Arda Ozcubukcu, discusses how the company is working to ensure psychedelic-assisted therapy is easily adopted by mainstream healthcare systems in the UK.

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Why we’re launching a free UK psychedelic therapist training programme

In recent weeks, much has been made of psychedelic drugs’ potential to redefine mental health treatment. As the sector becomes more visible, major players have started to re-evaluate their traditional roles within the psychedelic research ecosystem.

We’ve seen non-profit organisations like Multidisciplinary Association for Psychedelic Studies (MAPS) start to conduct clinical studies, an extremely uncommon phenomenon due to the vast amounts of funding required, as well as patient groups such as the Psychedelic Participant Advocacy Network (PsyPAN) influence the design of research processes.

Traditionally, a clinical research organisation’s (CRO) sole role is to action the research it has been commissioned to conduct. However, in a sector full of unknowns and firsts, where the necessary infrastructure is being established in real-time, a CRO has significantly more potential. Clerkenwell Health is on a mission to realise this potential, by redefining what a CRO can offer, and becoming a hub for innovation.

Discover how Clerkenwell Health is developing a gold standard for psychedelic care

As an emerging sector, psychedelic drug development faces a number of bottlenecks, and at Clerkenwell Health we don’t wait for others to solve problems, we tackle them head on.

The UK is fast becoming a central hub for psychedelic research thanks to the conducive regulatory environment brought about by post-Brexit sovereignty, which is attracting business and boosting innovation. Increasing numbers of psychedelic companies are moving their clinical operations to the UK, thus increasing the demand for psychedelic specialty therapists.

A major issue within the psychedelic research ecosystem is the lack of therapists able to deliver psychedelic-assisted therapy, which is an essential component to maximise the therapeutic benefits of psychedelics.

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With drugs now progressing to the later stages of development, clinical trials will require the delivery of psychedelic-assisted therapy at a much larger scale, increasing the demand for therapists even further. If sustainable ways of meeting this demand are not developed now, there will be serious capacity problems when these drugs hit the market.

Due to a lack of evidence showing which therapy model works with psychedelics most effectively, there are currently no standardised training opportunities provided by an independent body such as British Association for Counselling and Psychotherapy (BACP).

Limited therapy training opportunities exist, and those that do fail to fully consider the realities of the health system or the therapists who want to specialise in psychedelic therapy. Although some training programmes are offered by drug developers, it does not equip therapists to work across different compounds or disorders, whilst training run independent of developers can be expensive and time-consuming, making training accessible only to those who can afford the time and financial commitment. The situation, if it continues, will fail to create a workforce ready to deliver suitable psychedelic-assisted therapy at the scale required.

At Clerkenwell, our concern is that expensive programmes qualify therapists irrespective of their capabilities. That’s why we have designed a training programme that is free, disease- and compound-agnostic and minimises the time to commit for those interested to participate.

Our programme uses Acceptance and Commitment Therapy (ACT), a model that already has a solid evidence base and is practiced within the health system. This ensures the therapy aspect of psychedelic-assisted therapy is easily adopted by mainstream healthcare systems through medical and regulatory buy-in, which is vital for widespread patient access to these treatments.

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ACT seems to work effectively with psychedelics and using them together can maximise the therapeutic outcomes of both the therapy and the drug. Therapists can also keep their skills fresh by practicing ACT without psychedelics and are therefore more readily available to deliver psychedelic-assisted therapy post-marketing approval.

Scaling up psychedelic-assisted therapy is not an easy task, but one that is necessary for its successful adoption in the psychedelic research ecosystem. It’s time for the excitement of developing new psychedelic drugs to mature into developing delivery infrastructure, starting with the workforce.

As a CRO, Clerkenwell Health can help facilitate this process by paving the way for standardised certified training and acting as the cement that supports the psychedelic research ecosystem for different actors to build on. By investing in, innovating, and operating a centre of excellence for psychedelic-assisted therapy right in the heart of Europe’s most vibrant psychedelic research ecosystem, we can become the go-to partner for drug developers, regulators, and researchers who want to fundamentally change the face of mental health care.

Arda Ozcubukcu
Communications associate
Clerkenwell Health

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Bicycle Day: where are we 80 years since the first LSD trip?

On Bicycle Day 2022, we explore LSD’s journey from its first bicycle ride to MK Ultra to the treatment of addiction.

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Where are we 80 years since the first LSD trip?

In 1943, Swiss chemist Albert Hofmann took the first LSD trip – what is it looking like for the compound today?

Switzerland, 19 April, 1943. Chemist Albert Hofmann takes 250micrograms of LSD, proceeding to ride his bike as its effects kick in. So, Bicycle Day is born – a celebration of the first LSD trip.

Hofmann initially synthesised LSD from ergot in 1938 to use as an active pharmaceutical ingredient. Leaving the compound to one side, Hofmann decided to revisit it again in 1943. He felt a slight effect after accidentally absorbing a small amount of LSD through his fingertip three days before 19 April which led to the purposeful first trip. Hofmann later went on to describe the compound as “sacred”.

Since 1943, LSD has built up a rich history. Fuelling the countercultural revolution of the 1960s and animating the minds of great writers, poets, musicians and artists, LSD was previously researched for a number of different uses. 

One of the leading researchers was Stanislav Grof, who investigated the compound for its therapeutic use for different mental conditions and addiction. This research showed promising results, and as pointed out in a recent paper, reported limited adverse side effects.

However, the compound also had its dark side. It was used as part of the CIA’s secret MK Ultra programme (1953 – 1973). The programme looked at techniques such as hypnosis and used psychoactive substances for mind control and psychological torture tactics to harness against the Soviet Bloc during the Cold War.

In one experiment, “Operation Midnight Climax”, the CIA employed female sex workers to draw in men, when LSD would be used and the mens’ behaviour observed. Purportedly, renowned writer and psychedelic advocate, Ken Kesey, Acid Test pioneer, was also a volunteer in the MK Ultra programme. 

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Whilst Grateful Dead kept on truckin’ at their psychedelic concerts, and more young people began experimenting with psychedelic drugs, Nixon declared the worldwide “war on drugs” in 1971. Nixon labelled drug abuse as “America’s public enemy number one” leading to the scheduling of psychedelics in the highest category of the UN Convention on Psychotropic Substances. 

Since its scheduling, the last 50 years has seen a scientific censorship unknown in history. Scientists and researchers have been unable to investigate the compound, along with other psychedelics, for their potential therapeutic uses – despite previous research indicating they hold promise.

However, a handful of organisations and researchers have been able to overcome the regulatory and financial hurdles limiting access to compounds such as LSD, and now the world is beginning to see the blossoming of a new psychedelic era. 

This time, it is gearing towards the medical application of LSD. Although the cultural impact of psychedelics is easily seen, the spotlight is being put on the revolutionary potential of LSD and other psychedelics in helping the millions across the world living with poor mental health and addiction. From macrodosing to microdosing, LSD without the trip and assisted-psychotherapy, a new wave of scientific investigation is forming.

Discover some of the recent scientific research developments with LSD from Psychedelic Health: 

Study to explore effects of LSD microdosing
LSD findings could help understand how the brain generates behaviour
LSD trial for the treatment of adult ADHD initiated
New study to prevent unfounded LSD therapy patents
Novel findings presented on LSD and psilocybin

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Is psilocybin safe to administer under medical supervision? 

Drug Science has carried out a systematic review of adverse events reported in clinical trials.

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Is psilocybin safe to administer under medical supervision? 

Results from a systematic review have led to the conclusion that psilocybin is safe to administer in clinical settings, and that there is a need to revise the classification of psilocybin as a Schedule 1 substance.

Researchers at the UK non-profit Drug Science say their systematic analysis “strongly attests” to psilocybin’s safety.

Psilocybin is currently classed as a Schedule 1 under the United Nations Convention on Psychotropic Substances (1971). Any substance classified as a Schedule 1 substance fits the criteria of being highly addictive, having no therapeutic and having a lack of safety for use under medical supervision.

However, psilocybin is currently being administered in clinical settings for research exploring the compound’s efficacy as a therapy for mental health disorders and different addictions, such as nicotine dependence. 

More on research from Drug Science: The harms of psychedelics – separating anecdotes and misinformation

The systemic review from Drug Science investigated whether clinical trials of psilocybin support the third category of its Schedule I designation, that “there is a lack of accepted safety for use of the drug or other substance under medical supervision”.

The researchers analysed reports in the PubMed database for “adverse events, drug tolerability, and drug safety” stating that “while nearly all the publications reported behavioural and biological effects of the drug, these findings were not included in this review unless it was clearly stated to be an adverse event or safety risk.”

The results demonstrated that 25 of the 52 publications in the analysis did not contain any reference to adverse events, drug safety, or drug tolerability with 27 publications documenting administration of psilocybin on over 800 occasions to 550 individuals.

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The authors state that these 27 publications reported no serious or significant adverse events and positive drug tolerability, suggesting that “psilocybin is safe to administer under proper medical supervision”.

Of the adverse events that were reported, the authors state they were generally considered to be “transient and mild, the most common being headaches”, bar a handful of events that were considered to be more severe. However, the conclusions were that “psilocybin was not responsible for these events”.

The authors state: “The reviewed clinical trials demonstrated rigorous medical and psychological screening processes prior to participant enrollment. All studies excluded participants of vulnerable populations (e.g. history of psychosis), in order to avoid serious adverse events. 

“This practice is utilised for medications across all levels of scheduling, in the event that a drug may be safe and effective for certain populations, while having increased rates of adverse effects for others (e.g. one would not administer a beta-blocker to a hypotensive patient). 

“The participant selection criteria for many of the reviewed trials required prior experience with psychedelics, further screening out individuals who may be prone to psychedelic-related adverse events.”

They go on to say: “Considerable evidence suggests that psilocybin is generally well-tolerated when administered in a controlled setting. Federally and socially accepted selective serotonin reuptake inhibitors also pose a considerable level of risk, and the acceptable level of risk associated with psilocybin should not serve as a barrier to those whom it could provide positively life-altering outcomes.”

The authors also emphasise the role of set and setting as an important factor in the safe administration of psilocybin.

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Psychedelic Health is a journalist-led news site. Any views expressed by interviewees or commentators do not reflect our own. We do not provide medical advice or promote the personal use of psychedelic compounds. Please seek professional medical advice if you are concerned about any of the issues raised.

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