Beyond Healing: Exploring the Wider Potential of Psychedelic

In recent years, the conversation surrounding psychedelic substances has undergone a profound evolution. Once confined to the sidelines of medical science, psychedelics are now being recognised for their promising potential in treating various mental health disorders, including anxiety, depression, and addiction to tobacco and alcohol. Yet, this surge in interest goes beyond conventional psychiatric applications, as emerging research suggests that psychedelics like ayahuasca, psilocybin, and lysergic acid diethylamide (LSD) may offer benefits far beyond psychological well-being.1,2

Now, let us explore the myriad possibilities of psychedelics beyond the realm of mental health!

Inflammation and Infection

Ayahuasca, an Amazonian brew with psychoactive properties, has gained attention over the past two decades. Traditionally used in Ecuador, Colombia, Peru, and Brazil, it goes by various names such as natema, hoasca, daime, yagé, or yajé. The concoction involves boiling two plants: Banisteriopsis caapi, which contains β-carboline alkaloids like harmine and tetrahydroharmine, and Psychotria viridis, which provides the psychoactive alkaloid dimethyltryptamine (DMT).2

A systematic review conducted by Gonçalves et al. suggests that ayahuasca exhibits potential therapeutic benefits due to its anti-inflammatory and antimicrobial properties. Two studies explored the antimicrobial properties of ayahuasca: Bussmann et al. investigated the antibacterial effects of various plant extracts, finding promising activity in ethanol extracts of B. caapi against Escherichia coli and Staphylococcus aureus.3,4 Another study by Gonçalves et al. evaluated nine plant extracts for their antimicrobial effects against several bacterial strains. Notably, extracts of P. viridis, B. caapi, Peganum harmala, Mimosa hostilis, and a combination of M. hostilis and P. harmala inhibited bacterial growth across all tested strains. The extracts also showed anti-inflammatory activity, with promising results from P. harmala, M. hostilis, a combination of M. hostilis and P. harmala, and a commercial mixture.3,5 Overall, the findings from both studies suggest that ayahuasca possesses antimicrobial effects, making it a potential candidate for combating pathogenic microorganisms responsible for various infections.3

Furthermore, two more studies focusing on the anti-inflammatory properties of ayahuasca were indentified.3 Galvão-Coelho et al. conducted a clinical trial involving 45 healthy individuals and 28 patients with treatment-resistant depression to study the effects of ayahuasca on inflammation markers. They assessed C-reactive protein and interleukin 6 levels before and after ayahuasca ingestion. Prior to treatment, patients with depression had higher C-reactive protein levels than the control group. However, after ayahuasca treatment, there was a significant decrease in C-reactive protein levels.3,6 In another study, Liu et al. investigated the anti-inflammatory effects of β-carboline alkaloids found in P. harmala, a plant commonly used in ayahuasca preparation, using a nuclear factor-kB (NF-kB) reported assay. Results showed that harmol and harmine inhibited NF-kB transactivity. Harmine, in particular, showed promise by decreasing levels of inflammatory markers in cells and in a mouse model. These findings suggest that harmine might help reduce inflammation by stopping the NF-kB signalling pathway.3,7 While only a limited number of studies have explored the anti-inflammatory effects of ayahuasca, findings suggest that both ayahuasca extracts and certain β-carbolines found within it can reduce inflammation.3,6,7

In addition, Gonçalves et al. explored the potential of ayahuasca for skin healing. They assessed nine plant extracts used in ayahuasca preparation on the normal human dermal fibroblasts cell line. Through wound healing and permeability assays, they investigated the compounds’ effects on skin fibroblasts and their absorption. The findings showed that all samples promoted skin fibroblast migration without being absorbed, indicating significant healing potential in ayahuasca samples.3,8

Headache and Chronic Pain Disorders

Research on the therapeutic effects of psychedelic drugs for headache and chronic pain disorders has been ongoing for decades, with controlled studies now emerging. Many medications used to manage headaches share chemical or pharmacological similarities with psychedelic compounds, particularly in their structure and action on serotonin receptors. However, unlike conventional medications, psychedelics are noted for their ability to provide lasting preventive effects with minimal dosing in headache disorders.9

Most research on psychedelics in headache disorders focuses on cluster headaches, a rare condition often referred to as “suicide headache” due to the severity of pain experienced during attacks.9 Since the accidental discovery of psychedelics’ ability to suppress cluster headaches in the 1990s, patients have developed refined preventive treatments that work well for them. A common regimen involves a short course of low-dose psilocybin-containing mushroom, LSD, or lysergic acid amide-containing seeds, showing a significant and lasting reductions in cluster attack frequency.9,10—12

Migraine, affecting about 15% of the population, ranks among the most disabling disorders globally. Recently, Schindler et al. conducted a study with psilocybin, involving 10 patients who were dissatisfied with their current migraine treatment. The double-blind, placebo-controlled, cross-over study revealed significant reductions in migraine measures two weeks after a single dose, suggesting independence from psychotropic effects. They hypothesise that the immunomodulatory and anti-inflammatory properties of psychedelics play a role in migraine relief.9,13,14

Secondary chronic pain, like cancer-related pain, arises alongside other illnesses.14 Patients with advanced or terminal cancer commonly endure physical and psychological distress, with intense pain from tumour growth, treatment side effects, or immune responses.13,15 Cancer is frequently linked with adverse outcomes such as anxiety, depression, desire for hastened death, increased pain perception, and decreased quality of life, prompting the development of psychological interventions to alleviate existential distress and pharmacological interventions, like opioids, to manage pain. There is growing consideration that psychedelics may offer a potential means to address both the psychological and physical distress associated with cancer.13,16—18

In the 1960s, a pioneering study by Kast and Collins on the analgesic potential of LSD in 50 patients, mostly with terminal cancer, showed that LSD significantly reduced pain compared to opioids, indicating its ability to alter pain attention and perception. Kast expanded the research to 128 pre-terminally ill patients with metastatic cancer, observing that a single dose of LSD alleviated pain acutely and for up to two weeks, along with improvements in mood, reduced concerns about death, and better sleep; however, the patients also experienced mild hallucinations and anxiety.13,19 Research on psychedelic treatment in cancer patients has primarily focused on psychological factors, with studies exploring the therapeutic potential of LSD-assisted psychotherapy: Pahnke et al. found improvements in pain, mood, anxiety, and fear of death, with minimal adverse effects; Grof et al. observed relief from emotional distress, pain, and changes in attitude towards death, with analgesic effects lasting for weeks to several months; Kurland et al. emphasised the importance of reaching the “psychedelic peak experience” for optimal therapeutic effects in advanced cancer cases.13,20—22

Phase 3 trials with psilocybin-assisted psychotherapy are currently proposed in the United States and Europe, potentially marking a significant breakthrough for treating cancer patients. The treatment is expected to have rapid and sustained effects on psychological factors and may offer additional benefits for pain management.13

Brain Injury

Research suggests that psychedelics could revolutionise brain injury treatment. They work by decreasing inflammation in the brain, promoting the growth of new neurons in the hippocampus, enhancing neuroplasticity, and increasing the complexity of brain networks.23

Classical psychedelics primarily target the 5-hydroxytryptamine receptors in the brain, which not only induces their psychological effects but also holds potential for regulating inflammation in both the central nervous system and the body. Extensive research has focused on DMT for its effects on brain inflammation and reperfusion injury, and animal studies have shown that DMT can reduce ischemic brain injury after artery occlusion.23—25

Experimental traumatic brain injury in rodents has demonstrated acute loss of newly formed neurons in the hippocampus, a brain region associated with memory and learning.26 The growth of new neurons plays a vital role in traumatic brain injury and cognitive recovery.27 Administering psilocybin to mice, whether in low doses or high doses given weekly, has been found to increase the growth of new neurons in the hippocampus.28

Neuroplasticity refers to the brain’s remarkable ability to change and adapt to the environment, learning, memory, as well as rehabilitation after brain injury.29 In a case report, combining psilocybin with mirror therapy resulted in a reduction of phantom limb pain by enhancing the capacity to help “unlearn” paralysis through changes in neuroplasticity.30

Disorders of consciousness can occur due to various brain injuries such as trauma, hypoglycaemia, anoxia, and stroke.31 Scott and Carhart-Harris proposed testing psilocybin’s potential to increase consciousness in patients with disorders of consciousness. They suggest that psychedelics enhance brain activity complexity and conscious content, unlike stimulant drugs which primarily increase arousal.32

Despite decades of investigation, pharmacological treatment for brain injury is still in its early stages. Psychedelics show promise for future brain injury treatment, but further research is needed to fully understand their effectiveness and optimal usage.23

Benefits, Risks, and Considerations

With a growing interest in natural treatments amid concerns about adverse effects from conventional drugs, psychedelics emerge as a promising option. This is particularly important for individuals lacking access to advanced healthcare systems, as plant-based remedies may be their only available treatment option.3 Moreover, psychedelics have generally favourable safety profile and lower risk of addiction compared to opioids, offering a holistic approach to treatment by addressing both the physical and psychological aspects of the illness. This comprehensive approach may lead to long-lasting effects with minimal dosing, potentially providing effective options for conditions with limited treatment alternatives.9,13

However, careful consideration of safety and clear understanding of psychedelic’s acute and long-term effects are crucial to ensure their potential therapeutic benefits are realised and integrated effectively into medical practice.9 Generally, safety concerns regarding psychedelics primarily revolve around their psychological side effects like panic attacks and paranoia, commonly referred to as “bad trips”, which can pose risks to individuals and others, albeit rarely in controlled environments. Cases of prolonged psychosis after the use of psychedelics have also been reported, especially among those with pre-existing mental health illness or family history of mental illness.13,33,34

Additionally, the lack of regulatory approval for non-mental health indications raises legal and ethical concerns, and the limited research on the long-term effects and optimal dosing protocols further complicates the risk surrounding psychedelics. The encouraging news is that ongoing research initiatives are actively exploring these drugs to enhance our understanding of their mechanism, efficacy, and safety.2,9,13,23,35

Conclusion

In conclusion, the evolving conversation around psychedelic substances highlights their vast potential that extends beyond mental health treatments. Research indicates promising avenues for addressing conditions such as inflammation, pain, and brain injuries. Despite persistent challenges such as safety concerns and regulatory hurdles, ongoing research initiatives provide hope for advancing our understanding and unlocking new treatment options for patients in need. As we continue to explore the broader horizons of psychedelic therapy, the possibilities for healing and transformation are indeed boundless.

References:

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Author

Ivy Grace Rivera

Quality Control Manager & Senior Medical Writer