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Mixing psychedelics with lithium poses significant risk of seizures

The findings from the review showed that combining lithium with a classic psychedelic involved seizures in 47 per cent of 62 reports.

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Mixing psychedelics with lithium poses significant risk of seizures

A new review has suggested mixing classic psychedelics with lithium could pose a heightened risk of seizures.

The review of online trip reports documented on the websites Erowid, The Shroomery and Reddit, carried out by researchers at Johns Hopkins Centre for Psychedelic & Consciousness Research, has shown that mixing classic psychedelics, such as LSD or psilocybin, with the mood stabiliser lithium, could induce seizures in some individuals.

The findings from the review showed that combining lithium with a psychedelic involved seizures in 47 per cent of 62 reports, with 18 per cent resulting in “bad trips”, and 39 per cent involving medical attention.

Risk of seizures

A number of studies have shown that psychedelics hold promise for treating unipolar depression, however, the review highlights that patients living with bipolar disorder have been excluded from recent psychedelic trials.

MD, Post-Doctoral Research Fellow, at Johns Hopkins Centre for Psychedelic Research & Consciousness, Sandeep Nayak commented: “Mood stabilisers refer to drugs used to treat and prevent depression and mania in bipolar disorder. This typically refers to lithium and certain mood-stabilising, anti-seizure medications such as lamotrigine or valproate, but sometimes also refers to antipsychotics. 

“To my knowledge, there is not much research on this at all. People with bipolar disorder and seizure disorders are often excluded from modern psychedelic trials. I am aware of two cases of lithium use from an online survey in the 1990’s but that is it. There is good evidence from studies administering antipsychotics with psychedelics, and that was not the purview of this study. We looked at all mood-stabilisers, excluding antipsychotics, but only found sufficient reports of psychedelic use for lithium and lamotrigine.

“Roughly half of lithium reports involved seizures. This is a tonne, and was very surprising to me. In contrast, only ~2 per cent of all Erowid reports even mention the word “seizure”, and only a fraction of these would include people actually having them. Apart from seizures, an additional 18 per cent of lithium trips were considered “bad trips”. These are described as exceptionally bad, and often quite distinct from experiences when not on lithium.”

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In one anecdote cited in the report, an individual described a failed attempt at self-medicating with LSD. They said: “It was after finishing my exams, I was getting ready for Christmas vacation, was tired from studying but very relaxed and happy to have the chance to trip. I had a cold, I’d been taking over the counter cough syrup (Nyquil and Dayquil) which had apparently elevated my Lithium levels (I didn’t know there were certain over the counter drugs I was not supposed to take with Lithium). I took two hits of LSD that within 5 minutes it led to grand mal seizures that put me in the ICU for 3 days….”

It continued: “I’ve been told I stopped responding, fell off the couch, and starting seizing uncontrollably. I’m not sure how long the seizures lasted but from the ambulance report I was still having them all the way to the hospital and in the ER. I was given a spinal tap, cat scan, EKG, various drugs to stop the seizures, and admitted to the ICU where I stayed for 3 days. I remember bits and pieces from the ICU, and bits and pieces of the week following my release from the hospital. I had a lot of bruises, trouble walking, a very swollen chewed up tongue and was quite a mental and physical wreck for the next month, though conveniently it’s not well remembered.”

Another report included in the review cited: “I took lsd while on 900 mg of lithium and experienced the worst, most horrific trip of my life and haven’t touched lsd since. I had only taken 1 tab but the effects were akin to having doses 5 + tabs. I completely lost all touch with reality, everything I saw was drenched in blood, and I felt my throat closing up and felt like I was on fire-like my skin was burning. I somehow still managed to take a Seroquel despite having lost all touch with reality which brought me out of it after an hour or so I’m guessing (completely lost touch with time) and once I stopped hallucinating I was unable to speak for several hours.”

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Nayak highlighted that seizures with lithium were reported with LSD, psilocybin, 2C-I and 2C-C.

The dangers of self-medicating

Nayak noted that currently, there is a situation where people with a difficult to treat disorder, chiefly characterised by depressive episodes, such as bipolar disorder, read about exciting results from antidepressant trials of psilocybin which exclude people with their disorder and do not involve people taking mood stabilisers. 

“You can imagine this would lead some to try to treat themselves with psilocybin and exposing themselves to unknown risks,” Nayak said.

“Lamotrigine is relevant as a comparator, and of 34 reports, none were described as bad trips or seizures. In the majority (65 per cent) lamotrigine was not described as having effected the trip at all. In contrast, this was the case with lithium only 8 per cent of the time. Lamotrigine is an anti-seizure medication, so one could argue that ‘of course you won’t see seizures with lamotrigine’ for this reason, and that it is not really the lithium at all. This argument suggests that the kind of people who are likely to have seizures while using psychedelics and go on to write about it online were more likely to use lithium anyway. But I don’t think this is very plausible at all. In addition, there were four reports combining lithium and lamotrigine and in one someone reported a seizure. The remaining three were described as intensified.

“Online trip reports are not a good enough quality data source to establish safety or benefit, but I do think they are to establish some sense of potential harm, especially when better quality data is not forthcoming. So I think it is reasonable to conclude we should have concern about lithium and psychedelics, though this doesn’t mean lamotrigine is safe per se.”

See also  Funding acquired for psilocybin research for brain diseases

In order to improve understanding of the risk that psychedelics can pose to individuals who are taking mood stabilising drugs, Nayak says monitored dosing trials are an ideal starting point. 

“This is in the works for several drugs, including opioids and SSRIs, but also learning, in the form of studies like this or surveys, from the fact that people are already using psychedelics in combination with any number of other drugs. Ultimately, there will be psychedelic trials in people with bipolar disorder, and Josh Woolley at UCSF aims to do this, which I applaud.

“It’s really a unique situation,” added Nayak “where a drug is being investigated as a psychiatric treatment, but is already in widespread use all over the world. We should take advantage of the fact that people are already using psychedelic drugs and learn as much as we can from it.”

Nayak and his team currently have an ongoing survey of antidepressant use with psychedelics.

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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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