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Could psychedelics hold promise for brain injuries? 

Dr Evan Lewis at Numinus discusses psychedelics and sports-related traumatic brain injuries (TBIs).



Could psychedelics hold promise for brain injuries? 
Photo by Milad Fakurian on Unsplash

Psychedelics are being touted as a potential breakthrough in the area of mental health treatment. However, scientists are now beginning to look at whether the compounds could hold promise in the treatment of physical brain injuries. 

Around 3.8 million people acquire sports-related TBIs each year, with care for the injuries taking a multidisciplinary approach to rehabilitation and managing symptoms. Around 30 to 40% of patients with concussion symptoms live with significant mental health issues or functional neurological disorders.

Sports-related TBIs often have a different set of symptoms than non-sports-related TBIs. As opposed to concussions, TBIs cause damage at the cellular level and are associated with symptoms such as thought and sleep disruption, anxiety and depression, and other physical symptoms like balance issues and visual impairment.

With such a large range of symptoms associated with the injuries, treatment can be very expensive for healthcare systems. 

Dr Evan Lewis, concussion specialist and Vice President of Psychedelic Neurology at Numinus, is working to collect data on concussions and psychedelics to better understand if they are beneficial for TBIs, and to inform future research.

Psychedelics and sports-related brain injuries

While there is currently no clinical research that looks at using psychedelics for the treatment of TBIs, there is pre-clinical research that has so far demonstrated promising results – although they are few. 

Lewis, who predominantly works with chronic long-term concussion symptoms, told Psychedelic Health: “I think that it is very important to differentiate here between treatment with psychedelics for acute concussion versus treatment for chronic concussions – they are two different beasts.”

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Lewis highlights that there is a neuroinflammatory component to TBIs, and that there is also research looking at psychedelics for inflammation. For example, there is currently animal research investigating DMT for neuroinflammatory diseases such as Alzheimer’s, dementia and Parkinson’s disease.

Additionally, psychedelics have been shown to have an impact on neuroplasticity – how the brain makes new neuronal connections. Some psychedelic research has looked at an area of the brain called the hippocampus which is implicated in concussion injuries. 

Further literature around brain-derived neurotrophic factor (BDNF) and serotonergic psychedelics has shown increased markers of the regrowth of neurons – known as neurogenesis or synaptogenesis.

“When you look at mice data, we see that doses of psilocybin alter the way the hippocampus creates new connections,” said Lewis. “So that’s an important target. It also looks like serotonergic psychedelics show increased markers of the regrowth of neurons.”

Dr Lewis describes a chronic TBI as a “pressure wave” that shocks through the brain. The wave does not tear or damage any brain tissue, but causes disruptions at the cellular level – altering the connections between neurons. 

Lewis highlights that, as the brain functions as a network, these disruptions cause abnormal connections between networks. One network in particular that has been spotlighted in psychedelic research is the default mode network (DMN) where “over self-referential activity” takes place.

“This is a network that becomes connected when one is actively thinking about themselves,” said Dr Lewis. “In chronic brain injury, some of those areas have been shown to be affected. 

“This is where the crossover with psychedelics tends to happen as psychedelics relax the connections of the DMN. That relaxation in the DMN is some of the experiences people have with psychedelics such as oneness and ego dissolution.

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“After psychedelics, networks can become reconnected again. If TBIs cause problems with networking, we know psychedelics relax the networks and allow them to go into a neuroplastic state. With good guidance and therapy, networks can build back up again – could it be that this is the action of psychedelics in the context of concussion?” 

Lewis suggests that the window of neuroplasticity following psychedelic treatment should be taken advantage of, where TBI patients should work with a psychotherapists, physiotherapists and functional therapists. 

A network of data

Lewis is now working with Numinus to collect patient data and use the information to inform further research.

“We want to help patients who have chronic long-term concussion symptoms, who also have significant mental health issues,” said Lewis. “We want to help their mental health issues because we know that’s where psychedelics work. 

“As a secondary measure, I’m going to see if their concussion symptoms are improving. We’re planning to do this with about 10 patients, collect the data and then report that.”

Lewis suggests that there needs to be a higher level of interest from the concussion world about psychedelics, and more interest from the psychedelic world to incorporate brain injuries.

“Once that happens, the next step really is to work with the neuroradiologists and start to look at overlapping data,” said Lewis. “Once we have that information we will really have a great understanding about what we’re doing, because we know the mechanisms of psychedelics.”

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Is connection key? How clinicians impact patient outcomes in psychedelic therapy



A wealth of research is showing how psychedelic-assisted therapy holds promise for the treatment of mental health conditions such as depression, but what role does the therapist play in a patient’s outcome? A new study has suggested it may be a big one.

Psychedelics have piqued huge interest due to their effects on the brain. Research points to their ability to induce neuroplasticity in the brain as one of the key reasons they may help with conditions such as depression and anxiety.

However, set – the individual’s (or patient’s) mental state – and setting – the individual’s environment during a psychedelic experience – are hugely impactful on the outcome of these experiences.

In the traditional use of psychedelic medicines, shamans help to guide set and setting throughout the experience with singing, drumming and ritual. Today, in scientific research, trials, and in clinics, the clinician is essentially playing this role.

Senior author of a new study, Alan Davis, associate professor and director of the Center for Psychedelic Drug Research and Education in The Ohio State University College of Social Work, has highlighted that the impact of clinicians on patient outcomes is not new, with research consistently showing that a trusting relationship between patients and clinicians has been key to better outcomes. This concept is known as a “therapeutic alliance”.

Understanding the therapeutic alliance

To find out more about the impact of this therapeutic alliance in psychedelic therapy, researchers from Ohio State University College of Medicine analysed data from a clinical trial that investigated psilocybin-assisted psychotherapy for the treatment of major depressive disorder (MDD).

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In the trial, participants received two doses of psilocybin and 11 hours of psychotherapy, completing a therapeutic alliance questionnaire afterward, which assessed the strength of the therapist-participant relationship.

Participants also completed questionnaires about any mystical and psychologically insightful experiences they had during the drug treatment sessions. In psychedelic research, the mystical experience has often been shown to be related to the continuing positive effects of this therapy.

The Ohio team looked at the depression outcomes alongside patient reports about their experiences with the medicines as well as their connection with their therapists.

They found that a stronger relationship between patient and clinician led to a better clinical outcome for the patient – with improved depression scores up to 12 months following the experience.

Lead author Adam Levin, a psychiatry and behavioral health resident at Ohio State University College of Medicine, stated: “What persisted the most was the connection between the therapeutic alliance and long-term outcomes, which indicates the importance of a strong relationship.”

Analysis results revealed that over time, the alliance score increased, and in fact demonstrated more acute mystical experiences for the patient. The team also found that acute effects were linked to lower depression four weeks following treatment, but were not associated with better depression outcomes a year after the trial.

“The mystical experience, which is something that is most often reported as related to outcome, was not related to the depression scores at 12 months,” Davis stated.

“We’re not saying this means acute effects aren’t important – psychological insight was still predictive of improvement in the long term. But this does start to situate the importance and meaning of the therapeutic alliance alongside these more well-established effects that people talk about.”

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According to the team, the analysis showed that a stronger relationship during the final therapy preparation session predicted a more mystical and psychologically insightful experience – which in turn was linked to further strengthening the therapeutic alliance.

“That’s why I think the relationship has been shown to be impactful in this analysis – because, really, the whole intervention is designed for us to establish the trust and rapport that’s needed for someone to go into an alternative consciousness safely,” Davis stated.

“This isn’t a case where we should try to fit psychedelics into the existing psychiatric paradigm – I think the paradigm should expand to include what we’re learning from psychedelics,” Levin added.

“Our concern is that any effort to minimise therapeutic support could lead to safety concerns or adverse events. And what we showed in this study is evidence for the importance of the alliance in not just preventing those types of events, but also in optimizing therapeutic outcomes.”

The authors emphasised that efforts to minimise negative experiences in future studies of psychedelics is vital, and that therapy is critical to creating a supportive environment for patients.

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Phase 2a trial to investigate 5-MeO-DMT candidate for alcohol use disorder



Beckley Psytech and Clerkenwell Health are collaborating on a Phase 2a trial investigating Beckley’s synthetic 5-MeO-DMT candidate combined with psychological support as a treatment for alcohol use disorder (AUD).

AUD is estimated to affect around 237 million people across the globe and over 7.5 million people in the UK.

Treatment options for the harmful use of alcohol are not always effective – there are high relapse rates and there are around three million deaths each year attributed to the substance’s misuse.

Increasing research is showing that psychedelics may hold promise as innovative treatments for addiction, including substances such as ketamine and psilocybin.

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BPL-003 is Beckley Psytech’s short-duration and fast-acting synthetic formulation of 5-MeO-DMT – a psychedelic found in several plant species and the glands of at least one toad species – which is administered intranasally via an FDA-approved delivery device.

The compound has shown in Phase I data to be well-tolerated with a reproducible and dose-linear pharmacokinetic profile.

The Phase 2a trial

Beckley and Clerkenwell have confirmed that the collaborative Phase 2a open-label trial will evaluate the safety, tolerability and pharmacodynamic effects of a single dose of Beckley BPL-003 combined with abstinence-oriented psychological support in participants with AUD.

Currently taking place at King’s College London, Clerkenwell Health’s clinic near Harley Street, London, will provide an additional trial site.

According to Beckley, BPL-003 has been successful in eliciting psychedelic experiences of “similar intensity but shorter duration than psilocybin”.

Dr Henry Fisher, Chief Scientific Officer at Clerkenwell Health, stated: “An estimated 600,000 people are dependent on alcohol in England. This, coupled with an alarming increase in alcohol-related deaths of 89% over the past 20 years, shows the status quo isn’t working.

“Conventional treatments for alcohol dependency aren’t producing meaningful improvements and new avenues must be explored. This trial will assess whether psychedelic-assisted treatment can be an effective therapy for alcohol use disorder, with the hope of rolling out the treatment widely.

“Health professionals and policymakers should seriously consider such treatments, which could be genuinely ground-breaking for the NHS and for the hundreds of thousands of people being treated for alcohol use disorder in the UK.”

Beckley Psytech and Clerkenwell have emphasised that the results of the trial may be used to provide support for further study of psychedelic-assisted treatment for alcohol dependency.

Dr Rob Conley, Chief Medical and Scientific Officer at Beckley Psytech, added: “We’re committed to developing a transformative and effective treatment option for individuals struggling with alcohol use disorder.

“Based on our preclinical and Phase I data, we are optimistic about the potential therapeutic benefits of BPL-003 for substance use disorders and we are excited to evaluate the compound further in this clinical trial.

“I want to extend my thanks to the team at Clerkenwell Health and King’s, as well as to the patients who have joined, and will join, this study. Their participation, support and collaboration are absolutely critical to furthering research into this area of huge unmet need.”

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The Entourage Effect in Mushrooms: Natural psilocybin may outperform synthetic



The Entourage Effect in Mushrooms: Natural psilocybin may outperform synthetic

A new study from the Hebrew University-Hadassah Medical Center has indicated that natural psilocybin extracts may demonstrate superior efficacy to synthetic psilocybin extracts.

Recent years have seen a boom in research into psilocybin for the treatment of mental health conditions such as anxiety and depression.

Many of the clinical trials investigating psilocybin use synthetic extracts rather than natural ones. This is because synthetic extracts will contain psilocybin alone, whereas natural psilocybe mushroom extracts will contain several different compounds such as psilocybin, psilocin, baeocystin and norbaeocystin.

Having multiple compounds can pose a challenge when running clinical trials as identifying which compounds are active and what their impact is becomes difficult to measure, and the concentrations of these compounds can vary depending on factors such as growth conditions and processing techniques.

This makes the standardisation of multi-compound medicines a huge challenge, as medicine consistency, reproducibility and dosing become difficult. However, these are essential factors when it comes to conducting clinical trials and receiving approval for medicines from regulators.

The Entourage Effect

In 2011 Dr Ethan Russo put forward the theory of the Entourage Effect in cannabis. 

The cannabis plant contains over 400 different cannabinoids that have so far been identified, such as THC, CBD, CBN and CBG.

Russo hypothesised that these different cannabinoid compounds work synergistically to create a therapeutic effect, as opposed to compounds such as THC or CBD working in isolation.

This hypothesis has been touched on only a few times in the scientific literature in relation to psychedelic mushrooms.

For example, in Dr Jochen Gartz’s 1989 paper ‘Biotransformation of tryptamine derivatives in mycelial cultures of Psilocybe’ which proposed a synergistic relationship between compounds in the mushrooms, and a 2015 paper by Zhuck et al, ‘Research on Acute Toxicity and the Behavioral Effects of Methanolic Extract from Psilocybin Mushrooms and Psilocin in Mice’, which observed that the effect of psychedelic mushroom extracts on mice was much stronger than pure psilocybin.

There has been very limited research on this hypothesis in mushrooms since. 

A new study: Natural may outperform synthetic

Now, a research team from Hebrew University-Hadassah Medical Center BrainLabs Center for the Psychedelic Research have compared a natural psilocybin extract to a chemically synthesised version.

Published in Molecular Psychiatry, results from the study indicate that the natural extract increased the levels of synaptic proteins associated with neuroplasticity in key brain regions, including the frontal cortex, hippocampus, amygdala, and striatum.

The ability of psilocybin to induce neuralplasticity has been indicated as one of the key features that contribute to its therapeutic effects.

The researchers suggest that these new study results indicate that nautral psilocybin extracts may offer unique therapeutic effects that may not be not achievable with synthesised, single-compound psilocybin alone. 

Metabolomic analyses also revealed that the natural extract exhibited a distinct metabolic profile associated with oxidative stress and energy production pathways.

The researchers write: “In Western medicine, there has historically been a preference for isolating active compounds rather than utilising extracts, primarily for the sake of gaining better control over dosages and anticipating known effects during treatment. The challenge with working with extracts lay in the inability, in the past, to consistently produce the exact product with a consistent compound profile. 

“Contrastingly, ancient medicinal practices, particularly those attributing therapeutic benefits to psychedelic medicine, embraced the use of extracts or entire products, such as consuming the entire mushroom. Although Western medicine has long recognised the “entourage” effect associated with whole extracts, the significance of this approach has gained recent prominence.”

However, compared to cannabis, the researchers suggest that mushroom extracts present a unique case, as they are highly influenced by their growing environment such as substrate, light exposure temperature and more.

“Despite these influences, controlled cultivation allows for the taming of mushrooms, enabling the production of a replicable extract,” the team writes.

The researchers emphasise that this research underscores the superiority of extracts with diverse compounds, and also highlights the feasibility of incorporating them into Western medicine due to the controlled nature of mushroom cultivation.

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