The  2023 MAPS Psychedelic Science conference in Denver brought together hundreds of experts and enthusiasts to share their latest insights. Fascinated by the findings, we created a two-part series covering everything you need to know about the latest developments. 

Our first Psychedelic Science recap included cutting-edge research into microdosing, psilocybin therapies for depression, and diverse alkaloids across magic mushroom strains. Part two covers ketamine research, ayahuasca studies, and the latest on psychedelics for brain injuries and end-of-life anxiety. 

Let’s review. 

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1. Ketamine and psychedelics share the same antidepressant effects as traditional medications, yet they work faster and last longer. 

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Study 

“Antidepressant properties of ketamine and psychedelics: A common cellular pathway?”

Purpose & Methods 

Dr. Mark Rasenick and researchers at the University of Illinois at Chicago wanted to compare ketamine and traditional psychedelics to common antidepressants by investigating their cellular pathways. 

Dr. Rasenick first found that many antidepressants increase the movement of the G protein called Gs alpha, or Gsa, along the cell membrane. Previous research has demonstrated that antidepressant drugs collect gradually in cholesterol-rich membrane structures called “lipid rafts.” The team hypothesized that increased accumulation of Gsa in lipid rafts is a biomarker for depression, and Gsa relocating from those rafts is a biomarker for clinical responses to antidepressants. 

Dr. Rasenick’s team then compared antidepressants’ pharmacological action to psychedelics, like fluoxetine, ketamine, LSD, psilocin, and psilocybin. They analyzed cultured cells called “platelets” from 41 depressed subjects and 44 healthy controls. 

Summary of Findings 

• Antidepressants, psychedelics, and ketamine all show the same antidepressant biosignature: Gsa moving from lipid rafts and increased signaling of GPCRs (G-protein-coupled receptors, the largest and most diverse group of membrane receptors). 
• Like most antidepressants and ketamine, psychedelics treatment increased Gsa-activated cAMP response. (cAMP is an intracellular protein that regulates the expression of genes.)
• Stimulated cAMP signaling response in platelets was significantly lower in subjects with depression than in the healthy controls. 
• Psychedelics gave a prolonged (at least 24-hour) antidepressant biosignature.

Analysis 

Psychedelics and antidepressants have similar cellular signatures. However, they affect people in very different ways. 

Current depression medications are troublesome and often ineffective. Antidepressants can take approximately two months to work, and patients must continue taking these drugs for years. Weaning patients from these drugs can result in unpleasant symptoms ranging from flu-like feelings and persistent pain to Parkinson's-like conditions lasting for weeks. 

On the other hand, psychedelics like ketamine and LSD offer “rapid-acting” effects on an accelerated time scale, providing relief in as little as two hours after a single dose. 

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2. Psychedelics affect the whole brain as a complex system rather than single regions or networks. 

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Study

“A complex systems perspective on psychedelic brain action”

Purpose & Methods 

Researchers from McGill University and the University of California collaborated on a paper, advocating a novel perspective to decipher how psychedelics influence the brain.

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Previous neuroimaging studies demonstrated that psychedelics augment communication across extensive brain networks, a phenomenon termed “global integration.” Conversely, findings related to particular brain regions or networks have been inconsistent.

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In this 2023 paper, the team from McGill and UCLA introduce an innovative 'meta-perspective' to explain these inconsistencies and clarify the neurological effects of psychedelics.

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Arguments

• Instead of looking at how psychedelics affect individual parts of the brain, researchers argue for a "complex systems perspective." This “big picture” approach considers the brain a constantly changing system of interconnected parts.
• Based on this broader view, researchers suggest that psychedelics act as catalysts for whole-brain dynamical changes rather than region- or network-specific alterations.
• The team concludes that psychedelics’ “whole-system” action makes the brain more flexible, diverse, sensitive, and tuned for information sharing and propagation. 

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Analysis 

By positing that psychedelics induce a more dynamically flexible, diverse, and integrated mode of brain function, the authors create a new paradigm to explain their fascinating effects. This understanding is vital at a time when psychedelic-assisted therapy is showing potential transdiagnostic efficacy.

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3. Ayahuasca and psychedelics affect cell recovery in a way that has immense potential for traumatic brain injury. 

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Study 

“Ayahuasca for traumatic brain injury: Current trends and future possibilities”

Purpose & Methods 

The Center for Brain Injury and Repair (CBIR) wanted to know if psychedelics like Ayahuasca could help the brain repair from traumatic brain injury (TBI). So, they summarized the current state of science, showing that psychedelics target multiple facets of TBI neuropathy. Based on the findings, the team proposes a new experimental framework for exploring this theory further. 

Summary of Findings 

• Psychedelic pharmacotherapies may influence the future of brain injury treatment through modulation of neuroinflammation, hippocampal neurogenesis, neuroplasticity, and brain complexity.
• Psychedelics can drive extensive brain network remodeling, raising the ceiling for recovery. These compounds can also reduce blood-brain barrier permeability, making it easier for TBI treatments to reach targeted areas.
• Harmine, an alkaloid in Ayahuasca, can help remove glutamate from the brain. Excessive levels of glutamate, a neurotransmitter, contribute to various brain diseases, including Alzheimer's and Huntington's.
• DMT, another ayahuasca component, can help improve the function of mitochondria, the energy-providing parts of cells. This improvement can shield cells from two significant problems during recovery from traumatic brain injury (TBI): hypoxia, a situation where cells don't get enough oxygen, and excitotoxicity, a harmful condition where nerve cells die because there's too much glutamate. 

Analysis 

The field of pharmacologic treatment for brain injury is still in its early stages, even after decades of investigation. No pharmacotherapies have received FDA approval to enhance recovery or mitigate the chronic pathology of traumatic brain injury (TBI). Psychedelic compounds open a new avenue, offering a route for designing medications that could potentially address these injuries.

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4. Psychedelics and MDMA lead to improved meaning in life, correlating to higher happiness levels and less fear and sadness. 

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Study 

“Psychedelics, MDMA, and meaning in life”

Purpose & Methods 

Researchers at the Department of Psychology at Colorado State University created a study to measure how psychedelic use relates to meaning in life (MIL). They divided MIL into two main categories: presence of meaning (PM), or how much participants felt their lives had meaning, and search for meaning (SM), or how much participants felt their lives lacked purpose. 

The study data came via self-report surveys, which used the Meaning in Life Questionnaire to determine participants’ levels of PM and SM. The total number of participants was 2,595, with a mean age of 19.7. Researchers drew data on psychedelic use (LSD, psilocybin, and MDMA) from a more extensive survey called the Risky Behavior Inventory (RBI).

Summary of Findings 

• Lifetime psychedelic use led to higher levels of presence of meaning (PM) and lower levels of search for meaning (SM).
• Given these results, having ever taken a psychedelic or MDMA could positively affect how meaningful one’s life is. 
• Prior literature shows that PM correlates more with higher happiness levels, whereas SM correlates more with depression, fear, and sadness.

Analysis 

Individuals who have used psychedelics or MDMA often report increased happiness and decreased levels of depression, fear, and sadness. This observation could have significant implications for well-being and mental health treatment. However, correlation does not necessarily mean causation. More longitudinal research is needed.

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5. Group psilocybin psychotherapy is effective and can work faster, saving cancer patients and therapists significant time.

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Study 

“HOPE: A pilot study of psilocybin-enhanced group psychotherapy in patients with cancer”

Purpose & Methods 

The HOPE trial is a pilot study examining psilocybin-assisted group therapy in cancer patients with a DSM-5 depressive disorder, including major depressive disorder (MDD). 

The study involved three group preparatory sessions, one high-dose (25 mg) group psilocybin session, and three group integration sessions with cohorts of four participants over three weeks. Researchers collected clinical outcomes at a baseline, two weeks, and six months. 

Summary of Findings 

• Twelve participants completed the trial, and none reported severe adverse effects from psilocybin. 
• Measures of symptoms of depression showed a clinically substantial decrease for most patients from baseline to the two-week time point and the six-month time point.  
• Three out of 12 demonstrated a “clinically significant change” (4-6 points), and eight out of 12 showed a “clinically substantial change” (7-12 points).
• Six out of 12 participants met the criteria for remission at two weeks.

Analysis 

This pilot study demonstrated the safety, feasibility, and possible efficacy of psilocybin-assisted group therapy for cancer patients with depressive symptoms. A key note is that this study proved psychedelics can be effective and time-saving in helping depression symptoms, significantly reducing therapists’ and patients’ time compared to treatments without psychedelics. The findings warrant future investigations with the group therapy model.

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6. Psilocybin’s rapid anxiety and depression-relieving effects come partly from its ability to reduce pro-inflammatory cytokines.

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Study 

“Psilocybin induces acute and persisting alterations in immune status and the stress response in healthy volunteers.”

Purpose & Methods 

People suffering from stress-related disorders like depression, addiction, and PTSD often show elevated inflammation levels. As a result, experts theorize that inflammation-targeting drugs could improve mental health conditions.

Researchers at Yale conducted a placebo-controlled, parallel-group study to examine how psychedelics affect inflammation and stress activity. Sixty healthy participants received either a placebo or psilocybin. After seven days, they were divided further, with 15 in each group taking a stress or control test. 

The research team used ultra-high field magnetic resonance spectroscopy to assess changes in immune functioning. Patients also completed questionnaires that assessed changes in mood and social behavior.

Summary of Findings 

• Psilocybin reduced signs of inflammation in a time-dependent manner. 
• Immediately after taking psilocybin, researchers recorded a decrease in an inflammatory marker called TNF-α.
• A week later, TNF-α levels returned to normal, but other substances related to inflammation (IL-6 and CRP) remained lower in those who took psilocybin.
• Lowering TNF-α levels through psilocybin also led to a decrease in another depression-related substance, glutamate, in the hippocampus of the brain.
• A week later, the psilocybin group felt better and more social than the placebo group. 

Analysis 

These results align with other studies, indicating that inflammation correlates with mental health issues like social withdrawal, fatigue, loss of joy, and reduced appetite. Additionally, the study sheds light on why even a single dose of a psychedelic drug can alleviate stress-related disorders and reduce feelings of anxiety in healthy individuals. Psilocybin's lasting impact on inflammation markers might be a critical biological aspect of its consistent effects in combating depression.

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The Bottom line

Researchers at the 2023 MAPS Psychedelic Science conference unveiled groundbreaking insights that have opened new avenues for mental health understanding and treatment. Investigations into ketamine, ayahuasca, and psilocybin revealed how psychedelics influence the brain and mental well-being. These substances offer rapid-acting antidepressant effects, brain injury repair potential and enhanced life meaning. As mental health challenges escalate globally, psychedelic research is an exciting and critical frontier.

CTA: Contact ACS Laboratory for accurate qualitative and quantitative entheogen testing. We can test your psychedelic mushroom products if you have a DEA license. Please email info@acslab.com for more information.