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Ketamine’s therapeutic benefits go beyond depression, say researchers

Sub-anaesthetic does of ketamine could be beneficial for a number of different mental health conditions.

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Esketamine outperforms standard major depression treatment

New research has suggested that sub-anaesthetic doses of ketamine could be beneficial for conditions such as post-traumatic stress disorder (PTSD), anxiety, addiction and eating disorders.

Often used as an anaesthetic, research has shown ketamine is beneficial as a fast-acting anti-depressant. Recently, results from a randomised, controlled clinical trial, published in The British Medical Journal, also suggested that patients with suicidal ideation and bipolar disorder could also benefit from its rapid-acting effects.

Ketamine is also being researched as a helpful treatment for a number of different conditions such as gambling and alcohol addiction as well as anorexia nervosa. 

See also  Awakn initiates first ever ketamine treatment study for gambling addiction

Now, a new study from researchers at UBC Okanagan and the University of Exeter has found that the compound may well have benefits beyond its anti-depressant and anti-suicidal effects. The researchers say that ketamine could be “among the most significant developments in mental health treatment in decades.”

The findings serve as a foundation for researchers looking to design ketamine-related projects and offer valuable data for clinicians considering using ketamine with their patients.

Published in the British Journal of Psychiatry, the study analysed more than 150 studies on the effects sub-anaesthetic ketamine doses for the treatment of mental illness.

The study was led by psychology professor Dr Zach Walsh and doctoral student Joey Rootman at the Irving K. Barber Faculty of Arts and Social Sciences, and was co-led by professor Celia Morgan and doctoral student Merve Mollaahmetoglu from the University of Exeter.

See also  Ketamine-assisted therapy for alcohol addiction could save lives

Rootman stated: “We found strong evidence that indicates ketamine provides rapid and robust anti-depressant and anti-suicidal effects, but the effects were relatively short-lived. However, repeated dosing appeared to have the potential to increase the duration of positive effects.”

The evidence suggests ketamine may be helpful in the treatment of other disorders such as eating disorders, problematic substance use, PTSD and anxiety. However, the researchers point out that the evidence in these areas is scarce.

“What our research provides is an up-to-date overview and synthesis of where the knowledge on ketamine is at right now,” continued Rootman. 

“Our results signal that ketamine may indeed have a broader spectrum of potential applications in psychiatric treatment—and that tells us that more investigation is needed.”

See also  New findings on how ketamine prevents depression raise treatment hope

Walsh commented: “As many as one in five Canadians will experience a mental illness this year, and the reality is that existing treatments don’t work for everyone. As a result, many Canadians are curious about new approaches to help with these serious conditions.”

The study results provide some information to the public who are looking for these new approaches, says Walsh, who acknowledges that research into other treatment areas is also just beginning, but finds the preliminary evidence encouraging.

Walk added: “We need a lot more information on how these interventions could work — for example, administering the drug is only a part of treatment. We need to figure out what amount and type of psychotherapy would best complement the drug intervention to really maximise potential benefits.

“With that being said, it is a truly exciting time for ketamine research. If it can deliver the relief that early evidence suggests it can, this could be among the most significant developments in mental health treatment in decades.”

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Study identifies MDMA variants that could make therapy safer

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Study identifies MDMA variants that could make therapy safer

A new study from MedUni Vienna has identified three new variants of MDMA as promising alternatives for safer use in a controlled psychotherapeutic setting.

The recent blow to MDMA therapy from the FDA’s Psychopharmacologic Drugs Advisory Committee (PDAC) has put a dampener on many people’s hopes that the treatment would be approved this August.

While that still may happen, one of the major concerns of the advisory body was the compound’s safety data, and the PDAC has advised that Lykos has not collected enough safety data on the molecule in its trials so far.

See also  FDA MDMA therapy advice may be a setback, but it is not the end of the road

Despite this setback in the US, countries such as Canada and Australia have increased legal access to MDMA-assisted psychotherapy for PTSD in recent years.

However, there are concerns about the safety profile of the drug due to its side effects such as tachycardia, high blood pressure, and liver and nerve damage despite promising studies.

Safer alternatives

Now, published in the Journal of Neurochemistry, an international research team led by Harald Sitte at MedUni Vienna’s Center for Physiology and Pharmacology has identified three new variants of MDMA as promising alternatives for safer use.

According to the team, the variants – ODMA, TDMA and SeDMA – have been developed to retain the positive effects of MDMA while reducing negative effects.

The studies suggest that the variants impact structures in the brain such as serotonin and dopamine in a similar way to MDMA, but unlike MDMA, they have lower activity at certain serotonin receptors.

Study lead Harald Sitte stated: “This allows the conclusion that both the acute and long-term side effects of ODMA, TDMA and SeDMA may be lower than those of the conventional substance.”

“Since the MDMA analogues also have a weaker interaction with certain transport proteins in the body that are responsible for the absorption and excretion of drugs, the risk of interactions with other drugs could also be reduced,” added first author, Ana Sofia Alberto-Silva.

Sitte continued: “Our experimental results showed that the new variants can retain the therapeutic potential of the conventional substance, but are likely to cause fewer side effects.

“This could advance the controlled use of psychoactive substances in neuropsychiatric illness.”

The authors wrote: “Our findings suggest that these new MDMA bioisosteres might constitute appealing therapeutic alternatives to MDMA, sparing the primary pharmacological activity at hSERT, hDAT, and hNET, but displaying a reduced activity at 5-HT2A/2B/2C receptors and alternative hepatic metabolism. Whether these MDMA bioisosteres may pose lower risk alternatives to the clinically re-emerging MDMA warrants further studies.”

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

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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).

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.”

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

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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.

See also  How psychedelics could help those living with alcohol use disorders

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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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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