From Recreation to Rehabilitation: Exploring the Therapeutic Potential of Psychedelics

Get ready to dive deep into the intriguing world of psychedelic-assisted therapies, which are generating plenty of buzz in the mental health landscape. While we’ve only begun to scratch the surface of their potential, emerging research suggests psychedelics, including MDMA, ketamine, psilocybin, and LSD, may offer relief for various mental health conditions in a therapeutic setting.

Therapy with substance or Psychedelic-assisted therapy not only relies on the substance as a “cure-all” approach, rather the substance allows space for the therapy to delve into repressed, stuck or uncharted emotional waters. Psychedelic-assisted therapy (PAT), borrows from numerous therapeutic modalities. Drawing from eclectic techniques such as Internal Family Systems, somatic trauma therapies, and trauma-focused therapies, each approach aims to enhance psychological flexibility and deepen the spiritual, emotional, intellectual and  biomechanical effects of psychedelics.

In a time where traditional treatments often fall short, researchers are turning over every stone, and in this case, that stone might just be a “magic” mushroom.

MDMA (3,4-methylenedioxymethamphetamine):

Perhaps best known for its recreational use, is reemerging in the spotlight as a potential ally in the fight against PTSD. MDMA, often known as ecstasy, falls under a category called enactogens or empathogens. MDMA influences several neurochemical systems, including serotonin, dopamine, norepinephrine, cortisol, and oxytocin. In the controlled, nurturing environment of therapy, MDMA could assist by unlocking a profound emotional openness, reducing fear and defensiveness, and facilitating trust. It’s like the bridge that could reconnect patients with therapists, potentially leading to significant reductions in PTSD symptoms.

Ketamine

Ketamine, belonging to the family of dissociative anesthetics, can induce psychedelic effects at lower, non-anesthetic doses. Originally an anesthetic, ketamine is breaking barriers in treating depression, addiction, obsessive compulsive disorder (OCD), and PTSD. Its mechanisms are intriguing: blocking NMDA receptors, activating AMPA receptors, which in turn enhance synaptic plasticity and help control how your neurons, or brain cells, communicate with each other, especially in processes like learning and memory.

This unlikely hero has shown rapid antidepressant effects, creating new neural connections, kind of like rewiring a circuit board. But just like the precision required in electronics, we must approach Ketamine therapy with vigilance, considering long-term efficacy, safety, and optimal dosing protocols.

Psilocybin

The magic ingredient in certain species of mushrooms. Recently, it’s been showing promise in treating depression, anxiety, obsessive-compulsive disorder, and substance use disorders, and even end-of-life distress.

Working its magic on the serotonin system – serotonin 5-HT2A receptors, Psilocybin can promote neuroplasticity, enhance psychological flexibility, boost creativity, foster mindfulness, and encourage social connectedness. By inducing mystical experiences and shifting metaphysical beliefs, these substances may infuse life with renewed meaning and promote positive behavioral changes.

LSD (lysergic acid diethylamide):

A compound known for its dramatic effects on perception, cognition, and emotions. Although its therapeutic potential is still being uncovered, early hints suggest that LSD-assisted therapy might offer benefits in treating addiction, anxiety, and depression.  LSD acts on numerous serotonin receptors, altering neural activity and promoting altered states of consciousness, LSD could potentially add another dimension to therapy.

To make it easier to compare these substances at a glance, take a look at this overview guide of the uses, neuroscientific effects, experience and contraindications of each (resource: Beckley Academy; Foundations of Psychedelic Assisted Therapy. Module 3):

Effective and Promising Uses

Ketamine	Psilocybin	MDMA
Anti-depressant effects Reduction of suicidal thoughts PTSD Anxiety disorders Substance use disorders	Treatment-resistant depression Major depressive disorder Terminal cancer-related anxiety Obsessive compulsive disorder Alcohol and nicotine dependence	PTSD Depressive Symptoms

Mechanisms & Neuroscientific Effects

Ketamine	Psilocybin	MDMA
N-methyl-D-aspartate Receptor (NMDA) antagonist: increases synaptic transmission by increasing glutamate levels and neurotrophic factors that boost synaptic growth (Sattar et al., 2018) • Brain-derived neurotrophic factor (BDNF) boosts results in “…neurogenesis, the growth of new brain cells, and synaptogenesis, the formation of new connections between brain cells” (McShane in Miezio, 2022).	Acts on serotonin 5-HT2a receptors, correlated with the subjective effects of psychedelics (Madsen et al., 2019); Stimulates serotonin Receptors Inhibits posterior cingulate cortex & medial prefrontal cortex	Binding affinity to serotonin receptors that results in massive release of neurotransmitters (Mustafa et al., 2020) Increased serotonin, dopamine, noradrenaline; elevated hormones – oxytocin, vasopressin, cortisol, prolactin Symptoms; post experience serotonin depletion (Psychedelic Support, 2022) Inhibits amygdala (fear center)
Boosts in neuroplasticity (neurogenesis and synaptogenesis) (McShane in Miezio, 2022).	Increased neuroplasticity (synaptic growth and connections, expression of neuroplasticity related genes, and adaptive rewiring of neural circuits (Aleksandrova & Phillips, 2021; Ly et al., 2018; van Elk & Yaden, 2022)	Increased communication between amygdala and hippocampus (Psychedelic Support, 2022)

Timeline of Experience

	Ketamine	Psilocybin	MDMA
Onset	3 – 30 minutes dependent on dosing method	20-40 minutes	30 to 75 minutes
Peak	15 – 45 minutes	60-90 minutes	1 to 3 hours
Return	15 – 60 min. Gradual return to normal consciousness	30 – 60 min.	Trials typically offer a second dose around the 2-hr mark that extends the return.
Residual	60+ minutes	5 – 8 hours	Up to 7 days

Participant Experience – Positive

Ketamine	Psilocybin	MDMA
Muscle relaxation, pain relief, drowsiness Changes in perception, cognition, emotion Vivid imagery Altered auditory perception and proprioception Mood enhancement; feeling of awe/wonder Out-of-body experiences, ego dissolution, mystical experiences, death and rebirth experiences	Altered cognition, heightened emotions, heightened somatic experience Sensory synesthesia Vivid imagery; sounds; auditory and visual hallucinations Mood enhancement; feeling of expansiveness; connection with others and universe Out-of-body experiences, ego dissolution, mystical experiences, transcendence of space and time	Release of tension in the body Increased energy, alertness, arousal Temporary reduction of fear • Mood enhancement: Increased range of positive emotions (empathy, love, deep appreciation) Increased interpersonal trust Spiritual, transpersonal experiences

Participant Experience – Negative

Ketamine	Psilocybin	MDMA
Muscle trembles or jerks Decreased concentration, recall, recognition, and mental sharpness Double or blurred vision Increased intraocular eye pressure Increased blood pressure, heart rate Vomiting, dizziness Decreased conscious breathing Laryngospasm Blunted affect or emotional withdrawal Psychological distress, e.g., anxiety, paranoia, dysphoria, distorted perceptions of body and self	Muscle weakness, restlessness Confusion, disorientation Light sensitivity Headaches Nausea, vomiting, dizziness Irrational or reckless behavior • Flashbacks Psychological distress, e.g., anxiety, panic attacks, paranoia, dysphoria	Muscle tension, tremors, shaking Blurred vision Lack of appetite Sleep disturbances Sweating, hyperthermia Increased blood pressure Tachycardia Flashbacks Psychological distress, e.g., panic attack, confusion, brooding or rumination, depression, agitation

Contraindications

Ketamine	Psilocybin	MDMA
Hypertension Preeclampsia Eclampsia Severe cardiac disease Stroke Raised intracranial pressure Acute porphyria Epilepsy Schizophrenia Alcoholism	Cardiovascular issues Uncontrolled hypertension Pregnant/lactating Borderline Personality disorder Schizophrenia Bipolar disorder	Heart conditions Seizure disorders Pregnant /lactating Liver problems Malignant hypothermia Bipolar disorder

A Promising Future

The underlying biomechanical science is as fascinating as it is complex. These substances may induce neuroplasticity (think brain flexibility), modulate brain networks, and even trigger mystical-type experiences that could contribute to psychological insights, empathy, and a sense of connectedness. All of which may be grounds for life-changing and long-term therapeutic potential.

However, let’s not forget our due diligence. As exciting as these preliminary results may be, they’re based on limited studies. Widespread, robust research is crucial to establish safety, efficacy, optimal dosing, and long-term effects. Furthermore, professional supervision and appropriate screening are paramount to ensure we minimize risks and maximize benefits. As well as safety considerations and contraindications for various medications and particularly for individuals with pre-existing mental health conditions.

Psychedelic-assisted therapy is an exciting field that’s still in its infancy, as we rediscover the vast world of altered states of consciousness. With continued research and a measured approach, we can nurture its growth, exploring its potential in revolutionizing mental health treatment. As we do so, let’s remember to honor and integrate indigenous perspectives and ethical considerations to ensure a holistic approach to psychedelic therapy training. Stay tuned for more in this fascinating journey of discovery and healing.

Resources

• Aleksandrova, L. R., & Phillips, A. G. (2021). Neuroplasticity as a convergent mechanism of ketamine and classical psychedelics. Trends in Pharmacological Sciences, 42(11), 929–942. https://doi.org/10.1016/j.tips.2021.08.003
• Ardito, R., & Rabellino, D. (2011). Therapeutic alliance and outcome of psychotherapy: Historical excursus, measurements, and prospects for research. Frontiers in Psychology, 2270. https://doi.org/10.3389/fpsyg.2011.00270
• Bedi, G., Phan, K. L., Angstadt, M., & de Wit, H. (2009). Effects of MDMA on sociability and neural response to social threat and social reward. Psychopharmacology, 207(1), 73. https://doi.org/10.1007/s00213-009-1635-zf
• Bogenschutz, M. P., Forcehimes, A. A., Pommy, J. A., Wilcox, C. E., Barbosa, P., & Strassman, R. J. (2015). Psilocybin-assisted treatment for alcohol dependence: A proof-of-concept study. Journal of Psychopharmacology, 29(3), 289–299. https://doi.org/10.1177/0269881114565144
• Carhart-Harris, R. L. (2018). The entropic brain—Revisited. Neuropharmacology, 142, 167–178. https://doi.org/10.1016/j.neuropharm.2018.03.010
• Carhart-Harris, R. L., Bolstridge, M., Day, C. M. J., Rucker, J., Watts, R., Erritzoe, D. E., Kaelen, M., Giribaldi, B., Bloomfield, M., Pilling, S., Rickard, J. A., Forbes, B., Feilding, A., Taylor, D., Curran, H. V., & Nutt, D. J. (2018). Psilocybin with psychological support for treatment-resistant depression: Six-month follow-up. Psychopharmacology, 235(2), 399–408. https://doi.org/10.1007/s00213-017-4771-x
• Carhart-Harris, R. L., Bolstridge, M., Rucker, J., Day, C. M. J., Erritzoe, D., Kaelen, M., Bloomfield, M., Rickard, J. A., Forbes, B., Feilding, A., Taylor, D., Pilling, S., Curran, V. H., & Nutt, D. J. (2016). Psilocybin with psychological support for treatment-resistant depression: An open-label feasibility study. The Lancet Psychiatry, 3(7), 619–627. https://doi.org/10.1016/S2215-0366(16)30065-7
• Carhart-Harris, R. L., Erritzoe, D., Haijen, E., Kaelen, M., & Watts, R. (2018). Psychedelics and connectedness. Psychopharmacology, 235(2), 547–550. https://doi.org/10.1007/s00213-017-4779-2
• Carhart-Harris, R. L., & Goodwin, G. M. (2017). The therapeutic potential of psychedelic drugs: Past, present, and future. Neuropsychopharmacology, 42(11), 2105–2113. https://doi.org/10.1038/npp.2017.84
• Dolder, P. C., Schmid, Y., Müller, F., Borgwardt, S. J., & Liechti, M. E. (2017). LSD acutely impairs fear recognition and enhances emotional empathy and sociality. Neuropsychopharmacology, 42(11), 2318–2327. https://doi.org/10.1038/npp.2017.79