Research library

266 clinical studies, linked to source

Peer-reviewed research with plain-language summaries. Every entry links to the original publication — "trust us" is never the answer; "here's the data" is.

Psilocybin 85 compound profile →

Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning

Landmark Griffiths et al. 2006 study showing psilocybin produces mystical experiences with lasting personal and spiritual significance. One of the foundational modern psilocybin studies. Published in Psychopharmacology.

Psychedelics promote neuroplasticity through activation of intracellular 5-HT2A receptors

Vargas et al. 2023 Science paper discovering that psychedelics promote neuroplasticity via intracellular (not cell-surface) 5-HT2A receptors, explaining why serotonin doesn't trigger comparable effects.

Psilocybin as a Treatment for Psychiatric Illness: A Meta-Analysis

Irizarry et al. 2022 meta-analysis of 9 studies showing psilocybin improves symptoms in anxiety, depression, OCD, PTSD, and substance abuse. Published in Cureus.

Increased amygdala responses to emotional faces after psilocybin for treatment-resistant depression

Roseman et al. 2018 Neuropharmacology. fMRI study showing psilocybin increased (not decreased) amygdala responses to emotional faces in treatment-resistant depression, suggesting enhanced emotional processing rather than blunting.

Serotonin receptor involvement in acute effects of psilocybin in mice

Erkizia-Santamaría et al. 2022 study examining psilocybin's interaction with 5-HT2A, 5-HT2C, and 5-HT1A receptors and effects on thermoregulation. Published in Biomedicine & Pharmacotherapy.

Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels

Madsen et al. 2019 Neuropsychopharmacology. PET imaging study (n=15) showing psilocybin's subjective effects correlate with 5-HT2A receptor occupancy in the brain and plasma psilocin levels. Key pharmacokinetic data.

Acute Effects of Psilocybin After Escitalopram or Placebo Pretreatment in Healthy Subjects

Becker, Liechti et al. 2022 Clin Pharmacol Ther. RCT showing 14-day escitalopram pretreatment reduces psilocybin's subjective effects by 30-40%. Key safety data for SSRI interactions.

Extensive Collection of Psychotropic Mushrooms with Determination of Their Tryptamine Alkaloids

Gotvaldová et al. 2022 study quantifying psilocybin, psilocin, baeocystin, norbaeocystin, and aeruginascin in 226 mushroom samples. Key finding: tryptamine concentrations are extremely variable. Published in IJMS.

The neural basis of psychedelic action

Kwan et al. 2022 Nature Neuroscience review on how psilocybin, LSD, and mescaline produce effects via 5-HT2A receptor signaling, neuroplasticity, and brain network alterations.

Comparison of psychedelic and near-death experiences in changing attitudes about death

Sweeney/Griffiths et al. 2022 Johns Hopkins study of 3,192 participants comparing psychedelics (LSD, psilocybin, DMT, ayahuasca) with NDEs. ~90% reported decreased fear of death. Published in PLOS ONE.

Psilocybin produces substantial decreases in depression and anxiety in patients with life-threatening cancer

Griffiths et al. 2016 landmark Johns Hopkins RCT showing psilocybin produced sustained decreases in depression/anxiety in cancer patients. Published in Journal of Psychopharmacology.

Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial

Landmark Johns Hopkins RCT (Davis et al., 2021) showing psilocybin-assisted therapy produced large, rapid, and sustained antidepressant effects in patients with major depressive disorder. Published in JAMA Psychiatry.

Acute Physiological and Psychological Moderators of Psychedelic-induced Personality Change

Explores physiological and psychological moderators during psilocybin administration in healthy volunteers.

Effects of psychoplastogens on blood levels of BDNF in humans

Systematic review of psychoplastogens, including psilocybin, and their effects on brain-derived neurotrophic factor levels.

Psilocybin as a novel treatment for chronic pain

Investigates the potential of psilocybin as an anti-nociceptive agent for chronic pain treatment.

Neuroplasticity and Psychedelics

Comprehensive review of neuroplastic effects of classic psychedelics like psilocybin.

Synergistic Behavioral and Neuroplastic Effects of Psilocybin-NMDAR Modulator Administration

Study analyzing the synergistic effects of psilocybin combined with NMDA receptor modulators.

Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study

Carhart-Harris et al. 2016 landmark Lancet Psychiatry study - first modern clinical trial of psilocybin for depression. All 12 patients showed reduced depression symptoms at 1 week, with 67% in remission at 3 months.

Psychedelics Promote Structural and Functional Neural Plasticity

Ly, Olson et al. 2018 Cell Reports landmark paper showing DMT, LSD, and psilocin promote dendritic arbor complexity, spinogenesis, and synaptogenesis. Foundational evidence for psychedelic neuroplasticity.

Single-Dose Psilocybin Treatment for Major Depressive Disorder

Raison et al. 2023 JAMA Phase 2 RCT. Single 25mg synthetic psilocybin dose produced significantly reduced depression ratings vs placebo through 43 days in 104 participants.

The abuse potential of medical psilocybin according to the 8 factors of the Controlled Substances Act

Johnson, Griffiths et al. 2018 Neuropharmacology analysis. Systematic evaluation concluding psilocybin has low abuse potential, supporting rescheduling. Key policy paper.

Serotonin toxicity of serotonergic psychedelics

Malcolm & Thomas 2022 Psychopharmacology review examining serotonin syndrome risk with psychedelics. Key harm reduction paper on drug interactions with MAOIs, SSRIs, and other serotonergics.

Psychedelics not linked to mental health problems or suicidal behavior: A population study

Johansen & Krebs 2015 J Psychopharmacology landmark population study (N=135,000+). Found no associations between lifetime psychedelic use and mental health problems. Key safety evidence.

Pilot study of psilocybin in the treatment of tobacco addiction

Johnson, Griffiths et al. 2014 Johns Hopkins pilot study. 15 participants achieved 80% smoking abstinence at 6 months - far exceeding typical cessation rates. Published in J Psychopharmacology.

Long-term follow-up of psilocybin-assisted psychotherapy for cancer-related distress

Agin-Liebes et al. 2020 NYU long-term follow-up (4.5 years) of cancer patients. ~60-80% showed clinically significant reductions in anxiety/depression. Published in J Psychopharmacology.

Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms

Carhart-Harris et al. 2017 Scientific Reports. fMRI study showing psilocybin decreased amygdala blood flow and altered default mode network connectivity in treatment-resistant depression.

Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer

Ross et al. 2016 NYU RCT (companion to Griffiths study). Single psilocybin dose with psychotherapy reduced cancer-related anxiety/depression with 60-80% maintaining benefits at 6.5 months. Published in J Psychopharmacology.

Psilocybin therapy increases cognitive and neural flexibility in patients with major depressive disorder

Doss et al. 2021 Johns Hopkins Translational Psychiatry study. Psilocybin increased cognitive flexibility and reduced neural rigidity in depression, suggesting mechanism for therapeutic effects.

Psilocybin as a Treatment for Anorexia Nervosa: A Pilot Study Protocol

Spriggs, Carhart-Harris et al. 2021 Frontiers in Psychiatry. First study protocol for psilocybin treatment of anorexia nervosa, addressing rigid thought patterns and self-perception in eating disorders.

The relationships of classic psychedelic use with criminal behavior in the United States adult population

Hendricks et al. 2017 J Psychopharmacology population study. Classic psychedelic use associated with reduced odds of criminal behavior including theft, assault, and property crime.

Emotions and brain function are altered up to one month after a single high dose of psilocybin

Barrett, Griffiths et al. 2020 Scientific Reports. Single psilocybin dose produced sustained improvements in positive affect and reduced anxiety lasting at least one month.

Effects of psilocybin on cognitive and emotional functions in healthy participants: Phase 1 RCT

Rucker et al. 2022 J Psychopharmacology Phase 1 trial in healthy volunteers. Established safety profile and showed psilocybin effects on cognition and emotion without lasting impairment.

Subjective features of psilocybin experience: Double-blind comparison with dextromethorphan

Carbonaro, Griffiths et al. 2020 Psychopharmacology. Compared psilocybin to active placebo (DXM). Psilocybin produced unique mystical-type experiences not seen with DXM.

Positive expectations predict improved mental-health outcomes linked to psychedelic microdosing

Kaertner, Carhart-Harris et al. 2021 Scientific Reports. Showed microdosing benefits may be significantly influenced by expectation/placebo effects. Important for interpreting microdosing research.

Microdosing psychedelics: More questions than answers? An overview and suggestions for future research

Kuypers et al. 2019 J Psychopharmacol systematic review of microdosing research. Found mostly anecdotal evidence; called for rigorous RCTs examining potential risks of repeated low doses.

Microdosing psychedelics: Subjective benefits and challenges, substance testing behavior, and the relevance of intention

Petranker et al. 2020 J Psychopharmacol. Global Drug Survey (n=6,753) showing microdosers report benefits (mood, creativity) and challenges (illegal status, dosing uncertainty). Intention predicts outcomes.

Me, myself, bye: regional alterations in glutamate and the experience of ego dissolution with psilocybin

Mason, Kuypers, Ramaekers et al. 2020 Neuropsychopharmacology. MRS neuroimaging showing psilocybin reduces glutamate in hippocampus and prefrontal cortex, correlating with ego dissolution experience.

Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer

Ross, Bossis et al. 2016 J Psychopharmacol NYU RCT. Single-dose psilocybin with psychotherapy produced immediate and sustained decreases in anxiety and depression in cancer patients.

Efficacy and safety of psilocybin-assisted treatment for major depressive disorder: Prospective 12-month follow-up

Gukasyan, Davis et al. 2022 J Psychopharmacol. 12-month follow-up showing sustained antidepressant effects: 75% showing significant improvement, 58% achieving remission at 12 months.

Psilocybin with psychological support for treatment-resistant depression: six-month follow-up

Carhart-Harris et al. 2018 Psychopharmacology. Six-month follow-up to 2016 Lancet study showing sustained depression remission in treatment-resistant patients.

How do psychedelics work?

Carhart-Harris 2019 Current Opinion in Psychiatry review examining mechanisms of action underlying psychedelic effects: 5-HT2A activation, entropic brain theory, and therapeutic implications.

Psychedelics reopen the social reward learning critical period

Nardou, Dölen et al. 2023 Nature. Landmark study showing MDMA, LSD, psilocybin, ibogaine, and ketamine reopen critical period for social reward learning in mice. Duration of effect correlated with therapeutic potential.

Receptor-informed network control theory links LSD and psilocybin to a flattening of the brain's control energy landscape

Singleton, Carhart-Harris et al. 2022 Nature Communications. Shows LSD and psilocybin reduce brain control energy needed for state transitions using network control theory and 5-HT2A mapping.

Psychedelics in Psychiatry: Neuroplastic, Immunomodulatory, and Neurotransmitter Mechanisms

Inserra, Gobbi et al. 2021 Pharmacological Reviews comprehensive review. Examines mechanisms underlying psychedelic psychiatric applications including neuroplasticity, immunomodulation, and neurotransmitter effects.

Psilocybin-occasioned mystical-type experience in combination with meditation and other spiritual practices produces enduring positive changes

Griffiths, Johnson et al. 2018 J Psychopharmacology. Psilocybin combined with meditation/spiritual practices produced lasting improvements in psychological functioning and prosocial behaviors at 6-month follow-up.

Emotions and brain function are altered up to one month after a single high dose of psilocybin

Barrett, Doss et al. 2020 Scientific Reports. Single high-dose psilocybin produces enduring changes in affect and neural correlates in healthy volunteers persisting 1 month post-dose.

Lasting effects of a single psilocybin dose on resting-state functional connectivity in healthy individuals

McCulloch et al. 2022 J Psychopharmacology. Single psilocybin dose produced lasting changes in brain resting-state connectivity associated with positive clinical and wellbeing outcomes.

Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels

Madsen et al. 2019 Neuropsychopharmacology. PET imaging study showing psilocybin's subjective effects correlate with 5-HT2A receptor occupancy and plasma psilocin concentrations.

Brain serotonin 2A receptor binding predicts subjective temporal and mystical effects of psilocybin in healthy humans

Stenbaek et al. 2020 J Psychopharmacology. PET study showing individual differences in 5-HT2A receptor binding predict mystical-type experience intensity from psilocybin.

The hidden therapist: evidence for a central role of music in psychedelic therapy

Kaelen et al. 2018 Psychopharmacology. Shows music plays a central therapeutic role during psilocybin/LSD sessions, influencing emotional breakthroughs and treatment outcomes.

Validation of the Psychological Insight Scale: A new scale to assess psychological insight following a psychedelic experience

Peill, Carhart-Harris et al. 2022 J Psychopharmacology. Validated a new psychometric tool measuring psychological insight from psychedelic experiences. Insight predicted therapeutic outcomes.

Increased nature relatedness and decreased authoritarian political views after psilocybin for treatment-resistant depression

Lyons & Carhart-Harris 2018 J Psychopharmacology. Found psilocybin therapy significantly increased nature connectedness and decreased authoritarian political views in depression patients at 7-12 month follow-up.

Psilocybin: From Serendipity to Credibility?

Rucker & Young 2021 Frontiers in Psychiatry. Reviews psilocybin's therapeutic potential based on early-phase clinical trials and discusses ethical concerns about commercial psychedelic retreat centers.

Psychedelics, Meditation, and Self-Consciousness

Millière, Carhart-Harris et al. 2018 Frontiers in Psychology. Reviews how psychedelics and meditation alter self-consciousness through shared neurobiological mechanisms affecting sense of self and ego dissolution.

Serotonin and brain function: a tale of two receptors

Carhart-Harris & Nutt 2017 J Psychopharmacology. Landmark theory paper proposing psychedelics (5-HT2A agonists) enhance plasticity and active coping, contrasting with SSRIs (5-HT1A). Key framework for understanding psychedelic mechanisms.

Psychiatry & the psychedelic drugs. Past, present & future

Rucker, Iliff & Nutt 2018 Neuropharmacology. Comprehensive review of psychedelics in psychiatry covering history, current research on psilocybin/LSD/mescaline, and future therapeutic potential.

Increased global integration in the brain after psilocybin therapy for depression

Daws, Carhart-Harris et al. 2022 Nature Medicine. fMRI study showing psilocybin therapy increases brain network integration in depression, with changes correlating with symptom improvement.

Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression

Goodwin et al. 2022 NEJM. Large Phase 2b RCT (n=233) showing 25mg psilocybin produced significant depression reduction vs 1mg control at 3 weeks. First NEJM psilocybin trial.

A potential role for psilocybin in the treatment of obsessive-compulsive disorder

Jacobs 2020 J Psychedelic Studies. Review examining psilocybin's potential for OCD treatment based on serotonin 2A receptor agonism and preliminary clinical evidence.

Clinical treatment of cluster headache with psilocybin, LSD, and ketamine: A case series

Leighton et al. 2025 Cephalalgia Reports. Case series documenting successful treatment of cluster headache with serotonergic psychedelics and ketamine.

Benefits and harms of classical psychedelics for treating anxiety, depression, and existential distress in people with life-threatening diseases

Sharifan 2025 Cochrane Clinical Answers. Cochrane systematic review examining evidence for psilocybin and LSD in treating psychological distress in terminal illness.

Percentage of Heavy Drinking Days Following Psilocybin-Assisted Psychotherapy vs Placebo in the Treatment of Adult Patients With Alcohol Use Disorder

Bogenschutz, Ross et al. 2022 JAMA Psychiatry. Landmark RCT (n=93) showing psilocybin-assisted therapy significantly reduced heavy drinking days compared to placebo. First major trial for psilocybin in alcohol use disorder.

Acute change in functional brain entropy following psilocybin administration in healthy volunteers

McCulloch et al. 2022 Neuroscience Applied. Neuroimaging study showing psilocybin acutely increases brain entropy, providing mechanistic insights into psychedelic state.

Safety pharmacology of acute psilocybin administration in healthy participants

Straumann, Holze et al. 2024 Neuroscience Applied. Comprehensive safety/toxicity assessment of acute psilocybin showing favorable safety profile in healthy volunteers.

Mushroom, Psilocybin

Wiegand 2024 Encyclopedia of Toxicology. Comprehensive toxicology reference entry covering psilocybin mushroom identification, toxicity profile, clinical presentation, and treatment guidelines.

Effects of psilocybin, the 5-HT2A receptor agonist TCB-2, and the 5-HT2A receptor antagonist M100907 on visual attention in male mice

Rahbarnia et al. 2025 Psychopharmacology. Study examining how psilocybin's 5-HT2A receptor binding affects visual attention using selective agonists and antagonists.

Above the threshold, beyond the trip: the role of the 5-HT2A receptor in psychedelic-induced neuroplasticity and antidepressant effects

Drewko et al. 2025 Molecular Psychiatry. Review exploring how 5-HT2A receptor activation drives neuroplasticity and antidepressant effects of psychedelics.

In vitro assays for the functional characterization of (psychedelic) substances at the serotonin receptor 5-HT2A

Pottie & Stove 2022 J Neurochemistry. Methodological paper on in vitro assays for characterizing psychedelic binding and functional activity at 5-HT2A receptors.

Chemistry/structural biology of psychedelic drugs and their receptor(s)

Gumpper & Nichols 2024 Br J Pharmacology. Comprehensive review of psychedelic drug chemistry and structural biology of serotonin receptor binding.

Cerebral serotonin 2A receptor occupancy of psychedelic and non-psychedelic compounds measured in vivo in pigs

Madsen et al. 2023 Neuroscience Applied. PET imaging study comparing 5-HT2A receptor occupancy of psychedelic vs non-psychedelic compounds in vivo.

5-HT2A Receptor Heterodimerization

Łukasiewicz et al. 2018 5-HT2A Receptors in the CNS. Chapter on 5-HT2A receptor heterodimerization and implications for psychedelic signaling.

Psilocybin-assisted mindfulness training modulates self-consciousness and brain default mode network connectivity with lasting effects

Smigielski et al. 2019 NeuroImage. fMRI study showing psilocybin combined with mindfulness meditation produces lasting changes in DMN connectivity and self-consciousness.

From relaxed beliefs under psychedelics (REBUS) to revised beliefs after psychedelics (REBAS)

Zeifman et al. 2025 Scientific Reports. Empirical test of REBUS model showing psilocybin enables belief revision through relaxed high-level priors in brain hierarchy.

How psilocybin affects the brain

O'Leary 2024 Nature Medicine. News feature summarizing neuroimaging findings on psilocybin's effects on brain connectivity and neural networks.

Future directions for clinical psilocybin research: The relaxed symptom network

Lewis-Healey et al. 2022 Psychology & Neuroscience. Framework proposing psilocybin's therapeutic effects work through relaxing pathological symptom networks in the brain.

An introduction to psychedelic neuroscience

Calvey & Howells 2018 Progress in Brain Research. Foundational chapter introducing neuroimaging methods for studying psychedelic effects on brain function.

Psychedelic-Induced Neural Plasticity: A Comprehensive Review and Discussion of Clinical Implications

Weiss et al. 2025 Brain Sciences. Comprehensive review of neuroimaging evidence for psychedelic-induced neural plasticity and clinical applications.

Scanning the new frontier of mental health: psychedelic brain imaging

Ertl & Wall 2024 The Biochemist. Overview of neuroimaging techniques used to study psychedelic effects on brain activity and connectivity.

Classifying Unconscious, Psychedelic, and Neuropsychiatric Brain States with Functional Connectivity and Graph Theory

Jang et al. 2024 Brain Sciences. Neuroimaging analysis using graph theory to classify and compare brain states under psychedelics vs other altered states.

Mapping the claustrum to elucidate consciousness

Calarco 2024 Nature Reviews Psychology. Review of neuroimaging studies examining claustrum's role in consciousness, relevant to psychedelic mechanisms.

Hemispheric annealing and lateralization under psychedelics (HEALS): A novel hypothesis

Levin 2025 J Psychopharmacology. Novel neuroimaging-based hypothesis that psychedelics promote interhemispheric connectivity and reduce lateralization.

Comparing single- and repeat-dose psilocybin with active placebo for migraine prevention in an exploratory randomized controlled clinical trial

Schindler et al. 2025 Headache. Exploratory RCT comparing single and repeat psilocybin doses versus active placebo for migraine prevention.

Psilocybin for End-of-Life Anxiety Symptoms: A Systematic Review and Meta-Analysis

Yu et al. 2021 Psychiatry Investigation. Systematic review and meta-analysis of psilocybin trials for anxiety in terminal illness patients.

Psilocybin-assisted psychotherapy for cancer-related anxiety and depression

Yaniv et al. 2023 Int J Gynecological Cancer. Review of psilocybin-assisted psychotherapy trials for anxiety and depression in cancer patients.

A Modern Overview of the Potential Therapeutic Effects of Psilocybin in the Treatment of Depressive Disorders, Treatment-Resistant Depression, and End-of-Life Distress

Dino 2025 Cureus. Comprehensive overview of psilocybin clinical trials for depression, TRD, and end-of-life distress.

Ketamine 27 compound profile →

Dose-related effects of ketamine for antidepressant-resistant symptoms of PTSD in veterans

Landmark multi-center RCT (Abdallah et al., 2022) showing dose-related ketamine effects for treatment-resistant PTSD symptoms in veterans and active duty military. Published in Neuropsychopharmacology.

Personalized Use of Ketamine for Treatment-Resistant Depression

Nature Translational Psychiatry study on personalized ketamine dosing strategies for treatment-resistant depression.

Ketamine-assisted psychotherapy for trauma-exposed patients

Clinical chart review study examining ketamine-assisted psychotherapy outcomes in trauma-exposed patients.

The potential of ketamine for posttraumatic stress disorder: a review of clinical evidence

Liriano, Hatten & Schwartz 2023 review in Therapeutic Advances in Psychopharmacology synthesizing clinical evidence for ketamine in PTSD, including effects on symptom severity and the limits of current trial data.

The Role of Ketamine in Managing Depression and PTSD

Journal of Affective Disorders review of ketamine's role in depression and PTSD management.

Clinical Efficacy of Ketamine for Treatment-resistant Depression

Bratsos, Saleh 2019 Cureus. Systematic review examining ketamine efficacy in treatment-resistant major depressive disorder.

Adjunctive Intranasal Esketamine in Treatment-Resistant Depression

Daly et al. 2018 JAMA Psychiatry. Phase 2 RCT demonstrating intranasal esketamine efficacy for treatment-resistant depression, leading to FDA approval.

The psychotomimetic ketamine disrupts the transfer of late sensory information in the corticothalamic network

Qin et al. 2023 Eur J Neuroscience. Ketamine increases 'background noise' in thalamo-cortical system, potentially explaining psychosis-like symptoms.

Pharmacological and behavioral divergence of ketamine enantiomers: implications for abuse liability

Bonaventura et al. 2021 study showing S-ketamine (not R-ketamine) is responsible for abuse potential. Key for understanding esketamine vs racemic ketamine. Published in Molecular Psychiatry.

Comparison of antidepressant and side effects in mice after intranasal administration of (R,S)-ketamine, (R)-ketamine, and (S)-ketamine

Chang, Hashimoto et al. 2019 Pharmacol Biochem Behav. Preclinical comparison showing R-ketamine had greater antidepressant effect with fewer side effects than S-ketamine via intranasal route. Informs enantiomer selection.

Ketamine for suicidal ideation: A systematic review and meta-analysis

Witt et al. 2020 meta-analysis of 15 trials (572 participants) showing single ketamine infusion reduces suicidal thoughts for up to 72 hours. Published in ANZ J Psychiatry.

Ketamine for Rapid Reduction of Suicidal Thoughts in Major Depression

Grunebaum et al. 2018 American Journal of Psychiatry. Midazolam-controlled RCT showing ketamine rapidly reduced suicidal ideation within 24 hours in major depression. Key evidence for ketamine's anti-suicidal effects.

Intravenous Esketamine in Adult Treatment-Resistant Depression: A Double-Blind, Placebo-Controlled Study

Singh et al. 2016 Biological Psychiatry RCT establishing esketamine efficacy for treatment-resistant depression. Led to FDA approval of Spravato nasal spray.

Mechanisms of ketamine action as an antidepressant

Zanos & Gould 2018 Molecular Psychiatry comprehensive review of ketamine's antidepressant mechanisms including NMDA antagonism, AMPA potentiation, and neuroplasticity.

A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression

Zarate et al. 2006 landmark NIH study that launched ketamine depression research. First RCT showing single IV ketamine infusion produced rapid antidepressant effects within hours. Published in Arch Gen Psychiatry.

Ketamine Mechanism of Action: Separating the Wheat from the Chaff

Gould, Zanos, Zarate 2016 Neuropsychopharmacology. Comprehensive review dissecting ketamine's antidepressant mechanisms—NMDA antagonism, AMPA enhancement, mTOR signaling, and metabolite roles. Key mechanistic overview.

Rapid effectiveness of intravenous ketamine for ultraresistant depression in a clinical setting

Thomas et al. 2018 J Psychopharmacology. Real-world clinical evidence of IV ketamine effectiveness in ultraresistant depression. Identified anhedonia and bipolarity as clinical predictors.

Effects of Ketamine in Treatment-Refractory Obsessive-Compulsive Disorder

Bloch et al. 2012 Biological Psychiatry. First study of ketamine for treatment-refractory OCD showing rapid but transient anti-obsessional effects.

The Effect of a Single Dose of Intravenous Ketamine on Suicidal Ideation: A Systematic Review and Individual Participant Data Meta-Analysis

Wilkinson, Zarate et al. 2018 Am J Psychiatry. Meta-analysis showing single IV ketamine rapidly reduces suicidal ideation within hours, with effects lasting up to one week.

The rapid anti-suicidal ideation effect of ketamine: A systematic review

Hochschild, Grunebaum, Mann 2021 Preventive Medicine. Systematic review synthesizing evidence for ketamine's rapid anti-suicidal effects, examining onset, duration, and clinical implications.

A meta-analysis of the effects of ketamine on suicidal ideation in depression patients

Shen, Gao, Lv et al. 2024 Translational Psychiatry. Comprehensive meta-analysis examining ketamine's anti-suicidal effects across multiple trials in depressed patients.

Ketamine–NMDA receptor binding structure

Rogers 2021 Nature Reviews Neuroscience. Structural analysis of ketamine's binding to NMDA receptors revealed through cryo-EM imaging.

Glutamate and Glycine Binding to the NMDA Receptor

Yu & Bhatt 2018 Structure. Structural study of glutamate and glycine co-agonist binding to NMDA receptor, foundational for understanding ketamine's mechanism.

One-Year Outcomes Following Intravenous Ketamine Plus Digital Training Among Patients with Treatment-Resistant Depression

Price et al. 2023 JAMA Network Open. One-year follow-up of RCT showing sustained benefits of IV ketamine combined with digital cognitive training for TRD.

Insights for the Use of Ketamine From Randomized Controlled Trials That Compared Ketamine With Electroconvulsive Therapy in Severe Depression

Andrade 2022 J Clinical Psychiatry. Analysis of RCTs comparing ketamine to ECT for severe depression, providing clinical guidance.

High-dose Versus Low-dose Oral Ketamine on Control and Relapse of Treatment-resistant Depression: A Randomized, Double-blinded Clinical Trial

KheirAbadi & Golkar 2023 Iranian J Psychiatry and Behavioral Sciences. RCT comparing high vs low dose oral ketamine for TRD control and relapse prevention.

Efficacy of esketamine nasal spray for treatment-resistant depression: A meta-analysis of randomized controlled studies

Ouyang & Li 2025 Medicine. Meta-analysis of RCTs evaluating esketamine nasal spray efficacy for treatment-resistant depression.

LSD 24 compound profile →

Direct comparison of LSD and psilocybin in a double-blind placebo-controlled study

Holze et al. 2022 landmark study directly comparing LSD (100/200µg) and psilocybin (15/30mg) in 28 healthy volunteers. First rigorous head-to-head comparison. Published in Neuropsychopharmacology.

Increased Global Functional Connectivity Correlates with LSD-Induced Ego Dissolution

Tagliazucchi, Carhart-Harris et al. 2016 Current Biology. fMRI study showing LSD increases brain functional connectivity, with connectivity changes correlating with subjective ego dissolution experience.

LSD microdosing in major depressive disorder: results from an open-label trial

Muthukumaraswamy et al. 2026 Neuroscience Applied. Open-label trial examining LSD microdosing effects on major depressive disorder symptoms.

Role of the 5-HT2A Receptor in Acute Effects of LSD on Empathy and Circulating Oxytocin

Holze et al. 2021 Frontiers in Pharmacology. Demonstrates 5-HT2A receptor mediates LSD's prosocial effects on empathy and oxytocin release.

Pharmacological and non-pharmacological predictors of the LSD experience in healthy participants

Vizeli et al. 2024 Translational Psychiatry. Analysis of pharmacological and psychological predictors of LSD effects from nine placebo-controlled trials.

A low dose of LSD decreases pain perception in healthy volunteers

Ramaekers et al. 2020 study showing LSD 20µg significantly increased cold water tolerance time and reduced pain ratings. Published in Journal of Psychopharmacology.

Safety, tolerability, pharmacokinetics, and pharmacodynamics of low dose LSD in healthy older volunteers

Family et al. 2020 Psychopharmacology. First study of LSD (5-20µg) in older adults (55-75 years). Found low doses were well-tolerated with improved mood and cognition. Important for geriatric psychedelic research.

Self-blinding citizen science to explore psychedelic microdosing

Szigeti et al. 2021 landmark citizen science study with 191 participants. Found microdosing benefits may be explained by placebo effect. Published in eLife.

Crystal Structure of an LSD-Bound Human Serotonin Receptor

Wacker/Roth et al. 2017 landmark Cell paper revealing LSD's molecular binding to 5-HT2A/B receptors and why its effects last so long (receptor 'lid' mechanism).

Psychedelics Promote Structural and Functional Neural Plasticity

Ly, Olson et al. 2018 Cell Reports landmark paper showing LSD promotes dendritic arbor complexity, spinogenesis, and synaptogenesis. LSD was most potent of the compounds tested.

Neural correlates of the LSD experience revealed by multimodal neuroimaging

Carhart-Harris et al. 2016 PNAS landmark brain imaging study. First modern fMRI/MEG study of LSD showing increased brain connectivity, visual cortex activation, and ego dissolution neural correlates.

Microdosing psychedelics: More questions than answers? An overview and suggestions for future research

Kuypers, Nutt et al. 2019 J Psychopharmacology critical review of microdosing research. Highlights methodological gaps and proposes rigorous future research directions for LSD/psilocybin microdosing.

Low Doses of LSD Acutely Increase BDNF Blood Plasma Levels in Healthy Volunteers

Hutten, Mason et al. 2020 ACS Pharmacol Translat Sci. First study showing microdoses of LSD acutely increase BDNF (brain-derived neurotrophic factor) levels in humans.

LSD enhances suggestibility in healthy volunteers

Carhart-Harris et al. 2014 Psychopharmacology. Showed LSD increases suggestibility, potentially relevant to therapeutic applications combining psychedelics with psychotherapy.

LSD-assisted psychotherapy for anxiety associated with a life-threatening disease: A qualitative study of acute and sustained subjective effects

Gasser, Kirchner & Passie 2014 J Psychopharmacology. Qualitative 12-month follow-up of LSD therapy for end-of-life anxiety. 77.8% reported reduced anxiety, 66.7% improved quality of life. First modern LSD therapy study.

LSD alters eyes-closed functional connectivity within the early visual cortex in a retinotopic fashion

Roseman, Carhart-Harris et al. 2016 Human Brain Mapping. fMRI study showing LSD increases functional connectivity in visual cortex in a retinotopic pattern, explaining closed-eye visual hallucinations.

Is microdosing a placebo? A rapid review of low-dose LSD and psilocybin research

Polito, Liknaitzky 2024 J Psychopharmacology. Rapid review examining evidence for microdosing effects, finding limited placebo-controlled evidence but consistent self-report improvements.

LSD (lysergic acid diethylamide)

Howard, Stork 2024 Encyclopedia of Toxicology. Comprehensive toxicology reference entry covering LSD pharmacology, toxicity profile, clinical effects, and treatment guidelines.

Lysergic Acid Diethylamide (LSD) and the Heart: Exploring the Potential Impacts of LSD on Cardiovascular Function

Suleria et al. 2025 Cureus. Review examining LSD's cardiovascular effects including heart rate, blood pressure changes, and potential cardiac risks.

Are the LSD-analogs lisuride and ergotamine examples of non-hallucinogenic serotonin 5-HT2A receptor agonists?

Kehler & Lindskov 2025 J Psychopharmacology. Analysis of why some 5-HT2A agonists like lisuride produce therapeutic effects without hallucinogenic properties.

Acute effects of lysergic acid diethylamide on resting brain function

Müller et al. 2019 Swiss Medical Weekly. Neuroimaging review summarizing LSD's acute effects on resting-state brain function and network connectivity.

Dose-dependent LSD effects on cortical/thalamic and cerebellar activity: BOLD activity, underlying receptor changes, and behavioral correlates

Ghaw et al. 2024 Brain Communications. fMRI study showing dose-dependent LSD effects on cortical, thalamic, and cerebellar BOLD activity with receptor correlates.

Ketanserin reverses the acute effects of LSD in a randomized, double-blind, crossover study in healthy subjects

Becker et al. 2022 Neuroscience Applied. Neuroimaging study demonstrating 5-HT2A antagonist ketanserin blocks LSD's subjective and brain activity changes.

LSD microdosing in major depressive disorder: results from an open-label trial

Muthukumaraswamy 2026 Neuroscience Applied. Open-label trial of LSD microdosing for major depressive disorder showing preliminary efficacy data.

DMT 20

Human brain effects of DMT assessed via EEG-fMRI

Timmermann et al. 2023 PNAS study using combined EEG-fMRI to map DMT's effects on brain activity in 20 healthy volunteers. First study to capture DMT's neural signature with this methodology.

DMT alters cortical travelling waves

Alamia et al. 2020 eLife study showing DMT alters direction and magnitude of oscillatory travelling waves in visual cortex during eyes-closed states.

A Model for Target-Controlled Intravenous Infusion for Prolonged DMT Experience

Gallimore & Strassman 2016 paper proposing methodology for extended-state DMT research using anesthesiology infusion techniques. Published in Frontiers in Pharmacology.

The Therapeutic Potentials of Ayahuasca: Possible Effects against Various Diseases of Civilization

Frecska, Bokor, Winkelman 2016 Frontiers in Pharmacology. Comprehensive review of ayahuasca's potential therapeutic applications including depression, addiction, and autoimmune disorders. Discusses sigma-1 receptor mechanisms.

Effects of DMT on Mental Health Outcomes

Explores the impact of DMT on mental health, analyzing datasets from prospective studies.

Psychedelics Promote Structural and Functional Neural Plasticity

Ly, Olson et al. 2018 Cell Reports landmark paper showing DMT promotes dendritic arbor complexity, spinogenesis, and synaptogenesis comparable to ketamine. Foundational neuroplasticity evidence.

N,N-Dimethyltryptamine (DMT), an Endogenous Hallucinogen: Past, Present, and Future Research to Determine Its Role and Function

Barker 2018 Frontiers in Neuroscience comprehensive review of endogenous DMT research. Examines DMT biosynthesis in humans, its presence in brain tissue, and potential physiological roles.

Rapid antidepressant effects of ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial

Palhano-Fontes et al. 2018 Psychological Medicine first RCT of ayahuasca for depression. Showed significant antidepressant effects within 1-7 days in treatment-resistant patients.

Harmine produces antidepressant-like effects via restoration of astrocytic functions

Liu et al. 2017 study on harmine (MAO inhibitor in ayahuasca). Shows harmine has antidepressant effects by restoring astrocyte function, independent of DMT. Published in Prog Neuropsychopharmacol Biol Psychiatry.

N,N-dimethyltryptamine and the pineal gland: Separating fact from myth

Nichols 2017 critical review examining claims about pineal DMT. Concludes endogenous DMT concentrations are far too low to produce psychoactive effects. Important for scientific accuracy. Published in J Psychopharmacology.

Survey of entity encounter experiences occasioned by inhaled DMT

Davis, Griffiths et al. 2020 Johns Hopkins survey (N=2,561). Majority reported entity encounters during DMT experiences. 58% met criteria for 'mystical experience'. Published in J Psychopharmacology.

Chronic, Intermittent Microdoses of the Psychedelic N,N-Dimethyltryptamine (DMT) Produce Positive Effects on Mood and Anxiety in Rodents

Cameron, Olson et al. 2019 ACS Chemical Neuroscience. First study showing chronic microdosing with DMT produces positive mood and anxiety effects in rodents. Important for microdosing research.

Rapid and sustained decreases in suicidality following a single dose of ayahuasca among individuals with recurrent major depressive disorder

Zeifman et al. 2020 Psychopharmacology. Single-dose ayahuasca produced rapid and sustained reductions in suicidal ideation in treatment-resistant depression patients.

Neural correlates of the DMT experience assessed with multivariate EEG

Timmermann et al. 2019 Scientific Reports. EEG study revealing DMT increases oscillatory power at lower frequencies and increases signal diversity, correlating with subjective intensity.

Psychological and physiological effects of extended DMT

Luan, Rosas et al. 2023 PsyArXiv Preprint. First study using continuous IV infusion to maintain extended DMT state. Documented psychological and physiological effects over 30+ minutes.

Ayahuasca for the Treatment of Depression

Palhano-Fontes et al. 2021 Current Topics in Behavioral Neurosciences. Review of ayahuasca clinical trials for depression, including RCT evidence and neurobiological mechanisms.

Dimethyltryptamine (DMT) and ibogaine elicit membrane effects in HEK cells transiently transfected with the human 5-HT2A receptor

Eliasen et al. 2025 Brain Research. Study showing DMT and ibogaine produce distinct membrane effects via 5-HT2A receptor binding in transfected cells.

Potential therapeutic effects of an ayahuasca-inspired N,N-DMT and harmine formulation: a controlled trial in healthy subjects

Aicher et al. 2024 Frontiers in Psychiatry. Controlled trial testing ayahuasca-inspired DMT+harmine formulation in healthy volunteers for safety and acute effects.

Ayahuasca: pharmacology, safety, and therapeutic effects

dos Santos, Hallak 2025 CNS Spectrums. Comprehensive review of ayahuasca/DMT pharmacology, safety profile, toxicity data, and therapeutic applications.

Psychoactive effects and toxicity of tryptamine, N-methyltryptamine (NMT), and N,N-dimethyltryptamine (DMT): quantification methods

Paley 2021 Protein Biosynthesis Interference in Disease. Chapter on DMT toxicity, psychoactive effects, and analytical methods for quantifying tryptamines.

MDMA 20 compound profile →

MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study

Landmark Phase 3 RCT (Mitchell et al., 2021) demonstrating MDMA-assisted therapy for severe PTSD produced significant symptom reductions with favorable safety profile across multiple sites. Published in Nature Medicine.

MDMA-induced changes in within-network connectivity contradict the specificity of these alterations for serotonergic hallucinogens

Müller, Liechti et al. 2021 Neuropsychopharmacology. fMRI study showing MDMA alters brain network connectivity differently than classic psychedelics, highlighting distinct mechanisms of action.

MDMA-assisted psychotherapy for treatment of PTSD: pilot dose-response study

Mithoefer et al. 2018 J Psychopharmacol. Randomized pilot study (n=28) comparing MDMA doses (40mg, 100mg, 125mg) for chronic PTSD. Active doses showed greater symptom reduction; 76% no longer met PTSD criteria at 12-month follow-up.

MDMA-assisted psychotherapy for PTSD in veterans, firefighters, and police: a randomised, double-blind, dose-response, phase 2 clinical trial

Mithoefer et al. 2019 Psychopharmacology. Pooled analysis of six Phase 2 trials (n=103) showing MDMA-assisted therapy produced significant PTSD symptom reductions compared to placebo. Key data informing Phase 3 trial design.

MDMA for PTSD and beyond: a new paradigm brings hope

Shannon, Geller 2024 Frontiers in Human Neuroscience. Review discussing transformative potential of MDMA-assisted therapy for PTSD and related conditions.

The Psychotherapy in MDMA-Assisted Psychotherapy

Cristea et al. 2024 JAMA Psychiatry. Critical analysis of psychotherapy components in MDMA-assisted therapy and their contribution to treatment outcomes.

MDMA-assisted psychotherapy for treatment of chronic PTSD: A randomized phase 2 controlled trial

Ot'alora et al. 2018 Phase 2 RCT showing MDMA-assisted psychotherapy produced clinically significant reductions in chronic PTSD symptoms. Published in Journal of Psychopharmacology.

MDMA Impairs Both the Encoding and Retrieval of Emotional Recollections

Doss et al. 2018 Neuropsychopharmacology study showing MDMA impairs emotional memory encoding/retrieval. Relevant for understanding PTSD therapy mechanisms - may help reconsolidation of traumatic memories.

Reduction in social anxiety after MDMA-assisted psychotherapy with autistic adults

Danforth et al. 2018 Psychopharmacology pilot RCT showing MDMA-assisted therapy reduced social anxiety in autistic adults. First study of MDMA therapy in autism spectrum population.

First study of safety and tolerability of MDMA-assisted psychotherapy in patients with alcohol use disorder

Sessa et al. 2021 J Psychopharmacology. First study of MDMA-assisted therapy for alcohol dependence. Showed safety, tolerability, and promising efficacy signals in reducing drinking.

3,4-Methylenedioxymethamphetamine-assisted psychotherapy for treatment of chronic posttraumatic stress disorder: A randomized phase 2 controlled trial

Ot'alora et al. 2018 J Psychopharmacology MAPS Phase 2 RCT. MDMA-assisted psychotherapy for chronic PTSD showed significant symptom reduction with good safety profile.

Are ecstasy induced serotonergic alterations overestimated for the majority of users?

Szigeti, Winstock et al. 2018 J Psychopharmacology. Global Drug Survey analysis suggesting serotonergic neurotoxicity claims from MDMA use may be overstated for typical recreational users.

Multifaceted empathy of healthy volunteers after single doses of MDMA: A pooled sample of placebo-controlled studies

Kuypers, Liechti et al. 2017 J Psychopharmacology. Pooled analysis showing single MDMA doses enhance emotional empathy while cognitive empathy remains intact. Supports therapeutic mechanism for PTSD.

MDMA-assisted psychotherapy for treatment of anxiety and other psychological distress related to life-threatening illnesses: a randomized pilot study

Wolfson et al. 2020 Scientific Reports. MAPS pilot RCT showing MDMA-assisted therapy reduced anxiety in patients with life-threatening illnesses. First study extending MDMA therapy beyond PTSD.

Neurotoxicity of MDMA: Main effects and mechanisms

Costa, Gołembiowska 2022 Experimental Neurology. Comprehensive review of MDMA neurotoxicity mechanisms including serotonergic damage, oxidative stress, hyperthermia, and therapeutic implications.

Caffeine and MDMA (Ecstasy) Exacerbate ER Stress Triggered by Hyperthermia

Trychta, Harvey 2022 Int J Mol Sci. Research showing caffeine combined with MDMA worsens hyperthermia-induced cellular stress, important safety data for polydrug use scenarios.

Allosteric Binding of MDMA to the Human Serotonin Transporter (hSERT) via Ensemble Binding Space Analysis

Islas & Scior 2022 Molecules. Computational study revealing MDMA's allosteric binding mechanism at human serotonin transporter using induced fit docking and Monte Carlo simulations.

Role of Serotonin Transporter and Receptor Gene Variations in the Acute Effects of MDMA in Healthy Subjects

Vizeli et al. 2019 ACS Chem Neuroscience. Pharmacogenetic study showing how genetic variations in serotonin transporter and receptors affect individual MDMA response.

MDMA-assisted therapy for PTSD passes phase III trial

Mullard 2023 Nature Reviews Drug Discovery. News coverage of MDMA-assisted therapy Phase III success for PTSD treatment.

The METEMP protocol: Massed exposure therapy enhanced with MDMA for PTSD

Maples-Keller et al. 2025 Contemporary Clinical Trials Communications. Protocol paper for clinical trial combining massed exposure therapy with MDMA for PTSD.

5-MeO-DMT 11 compound profile →

5-MeO-DMT modifies innate behaviors and promotes structural neural plasticity in mice

Jefferson et al. 2023 Neuropsychopharmacology study showing 5-MeO-DMT affects behavioral patterns and promotes dendritic spine growth in rodent brain tissue.

Fear as medicine: A mixed-methods analysis of 5-MeO-DMT, mental health, and intergenerational healing

Overall 2025 Applied Psychology Research. Mixed-methods analysis examining 5-MeO-DMT's role in mental health and intergenerational healing processes.

A Toad Less Traveled: Should 5-MeO-DMT Have a Role in Treating Depression?

Hayes 2025 Psychedelic Medicine. Review examining evidence for 5-MeO-DMT in depression treatment and its therapeutic potential.

Psychedelic treatment for alcohol misuse and PTSD in Special Operations Forces Veterans

Armstrong et al. 2023 Military Psychology study on psychedelic-assisted treatment for co-occurring alcohol misuse and PTSD in US Special Operations Forces Veterans.

Single inhalation of 5-MeO-DMT: Sustained enhancement of satisfaction with life and decrement of psychopathological symptoms

Uthaug et al. 2019 Psychopharmacology naturalistic study. Single vapor inhalation of toad-derived 5-MeO-DMT related to lasting improvements in life satisfaction and mindfulness.

Innovative Psychedelic Therapies: Harnessing 5-MeO-DMT and DMT for Mental Health Treatment

Kargbo 2024 ACS Medicinal Chemistry Letters. Review of 5-MeO-DMT and DMT therapeutic potential, covering pharmacology, clinical development, and mental health applications.

Intensity of Mystical Experiences Occasioned by 5-MeO-DMT and Comparison With a Prior Psilocybin Study

Barsuglia, Davis et al. 2018 Frontiers in Psychology. Showed 5-MeO-DMT produces mystical experiences comparable in intensity to high-dose psilocybin, with potential therapeutic implications.

Use of Benefit Enhancement Strategies among 5-Methoxy-N,N-Dimethyltryptamine (5-MeO-DMT) Users: Associations with Mystical, Challenging, and Enduring Effects

Lancelotta, Davis 2020 J Psychoactive Drugs. Survey examining how preparation and integration practices affect 5-MeO-DMT outcomes and long-term benefits.

5-MeO-DMT has not been found in traditional ayahuasca preparations and the combination of 5-MeO-DMT with MAOIs is dangerous

Lancelotta 2022 Human Psychopharmacology. Critical safety warning about lethal risks of combining 5-MeO-DMT with MAOIs, clarifying 5-MeO-DMT is not present in traditional ayahuasca.

A Toad Less Traveled: Should 5-MeO-DMT Have a Role in Treating Depression?

Hayes 2025 Psychedelic Medicine. Commentary exploring the therapeutic potential of 5-MeO-DMT for depression treatment.

Innovative Psychedelic Therapies: Harnessing 5-MeO-DMT and DMT for Mental Health Treatment

Kargbo 2024 ACS Medicinal Chemistry Letters. Review of therapeutic applications of 5-MeO-DMT and DMT for mental health treatment.

THC 7 compound profile →

Ingestion of a THC-Rich Cannabis Oil in People with Fibromyalgia: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

Chaves et al. 2020 Pain Medicine. RCT showing THC-rich cannabis oil significantly reduced pain and improved quality of life in fibromyalgia patients.

Cannabis, a cause for anxiety? A critical appraisal of the anxiogenic and anxiolytic properties

Sharpe et al. 2020 J Translational Medicine. Critical appraisal of cannabis anxiolytic vs anxiogenic effects with clinical implications for anxiety disorders.

THC, CBD, and Anxiety: a Review of Recent Findings on the Anxiolytic and Anxiogenic Effects of Cannabis' Primary Cannabinoids

Lichenstein 2022 Current Addiction Reports. Review of dose-dependent anxiolytic and anxiogenic effects of THC and CBD from recent literature.

Acute Cannabis Toxicity

2019 Pediatric Emergency Care. Clinical review of acute cannabis toxicity presentations in pediatric and adult patients, treatment guidelines, and emerging trends.

Serotonin Syndrome versus Cannabis Toxicity in the Emergency Department

Baltz, Le 2020 Clinical Practice and Cases in Emergency Medicine. Case report distinguishing cannabis toxicity from serotonin syndrome, important for differential diagnosis.

Cannabinoid CB1 and CB2 Receptor-Mediated Arrestin Translocation: Species, Subtype, and Agonist-Dependence

Ibsen et al. 2019 Frontiers in Pharmacology. Study of CB1 and CB2 receptor signaling via arrestin translocation across species and agonist types.

Cannabinoid receptor CB1 and CB2 interacting proteins: Techniques, progress and perspectives

2021 Methods in Cell Biology. Review of protein-protein interactions at cannabinoid receptors and implications for signal transduction.

Alcohol 7 compound profile →

Neuropharmacology of Alcohol Addiction

Vengeliene et al. 2008 comprehensive review of alcohol's effects on mesolimbic dopamine, GABA, glutamate, serotonin, and opioid systems. Explains how chronic use recruits anti-reward/stress mechanisms driving compulsive drinking. Published in British Journal of Pharmacology.

Clinical management of the alcohol withdrawal syndrome

Jesse et al. 2021 clinical review of alcohol withdrawal management including seizure risk, delirium tremens, and evidence-based pharmacotherapy with benzodiazepines and anticonvulsants. Published in Drugs.

Alcohol Use Disorder: Neurobiology and Therapeutics

Mukherjee 2022 review covering alcohol's multi-system neurotoxicity, epigenetic modifications, neuroinflammation, and gut-brain axis disruption. Covers FDA-approved treatments: naltrexone, acamprosate, and disulfiram. Published in Biomedicines.

Promising strategies for the prevention of alcohol-related brain damage through optimised management of acute alcohol withdrawal

2024 literature review on how repeated withdrawal episodes (kindling) cause cumulative brain damage. Optimized acute withdrawal management may prevent long-term cognitive decline and Wernicke-Korsakoff syndrome.

Neurotoxicity and neurocognitive impairments with alcohol and drug-use disorders: potential roles in addiction and recovery

Bates et al. 2002 review of how alcohol-induced neurotoxicity causes measurable cognitive impairment affecting executive function, memory, and visuospatial abilities, with implications for treatment outcomes.

Glutamate Receptor-Mediated Neurotoxicity in a Model of Ethanol Dependence and Withdrawal

Reynolds et al. 2019 study demonstrating that ethanol withdrawal causes dose-dependent hippocampal neuron death via AMPA and mGluR5 glutamate receptors. AMPA antagonists attenuated toxicity, suggesting neuroprotective treatment targets.

Investigating Therapeutic Targets for Alcohol Use Disorder: Pharmacological View of ClinicalTrials.gov Data

2025 systematic analysis of ClinicalTrials.gov registrations for AUD treatments. Maps the landscape of GABAergic, glutamatergic, opioidergic, and serotonergic targets being pursued in active clinical trials.

Ibogaine 6 compound profile →

Ibogaine: Revisiting an Ancient Alkaloid for Modern Opioid Dependence

Moore et al. 2025 Substance Use & Misuse. Review examining ibogaine's pharmacology and clinical evidence for treating opioid dependence.

Ibogaine Detoxification Transitions Opioid and Cocaine Abusers Between Dependence and Abstinence: Clinical Observations and Treatment Outcomes

Mash et al. 2018 Frontiers in Pharmacology. Clinical observations showing ibogaine detoxification effectively transitions opioid/cocaine users toward abstinence.

Safety of ibogaine administration in detoxification of opioid-dependent individuals

Knuijver, Schellekens et al. 2022 Addiction. Open-label observational study (n=14) evaluating ibogaine safety during opioid detoxification. Documented cardiac monitoring protocols and outcomes.

Ibogaine/Noribogaine in the Treatment of Substance Use Disorders: A Systematic Review of the Current Literature

Mosca, Chiappini et al. 2023 Current Neuropharmacology. Systematic review of ibogaine and noribogaine clinical evidence for treating substance use disorders.

Response to Luz & Mash on cardiac toxicity of ibogaine

Schellekens, Kramers et al. 2022 Addiction. Analysis of ibogaine cardiac toxicity including QT prolongation and arrhythmia risk. Important safety data for ibogaine treatment protocols.

Multiple Episodes of Cardiac Arrest Induced by Treatment With Ibogaine: A Case Report

Mestre et al. 2024 Cureus. Case report documenting multiple cardiac arrests during ibogaine treatment, highlighting critical cardiac safety concerns and monitoring requirements.

Kratom 6 compound profile →

Kratom as a substitute for opioids: Results from an online survey

Coe et al. 2019 Drug Alcohol Dependence. Large survey (n=2,798) showing kratom users primarily use it to manage pain and opioid withdrawal, with low reported adverse effects.

Understanding the Effects and Clinical Potential of Kratom (Mitragyna speciosa): A Narrative Review

2025 Bangkok Medical Journal. Narrative review examining kratom's pharmacology, clinical potential, and safety considerations.

Forensic Implications of Kratom: Kratom Toxicity, Correlation with Mitragynine Concentrations, and Polypharmacy

Papsun et al. 2023 Current Addiction Reports. Forensic analysis of kratom toxicity cases, mitragynine lethal concentrations, and polydrug interactions.

Kratom-Associated Fatalities in Northern Nevada—What Mitragynine Level Is Fatal?

Schmitt et al. 2021 Am J Forensic Med Pathol. Analysis of kratom-associated deaths examining fatal mitragynine blood concentrations and LD50 implications.

Fatal Mitragynine-Associated Toxicity in Canada

Wang, Walker 2018 Academic Forensic Pathology. First documented fatal kratom/mitragynine toxicity case in Canada, establishing baseline lethal dose data.

Kratom Alkaloid Mitragynine: Inhibition of Chemotherapy-Induced Peripheral Neuropathy in Mice via Adrenergic and Opioid Receptors

Farkas et al. 2022 SSRN. Study showing mitragynine's analgesic effects depend on both adrenergic and opioid receptor activation, with sex-dependent variations.

Cocaine 6 compound profile →

Cocaine and Cardiotoxicity: A Literature Review

Havakuk et al. 2021 review of cocaine's cardiac effects including coronary vasospasm, arrhythmias, cardiomyopathy, and aortic dissection. Cocaine causes irreversible structural heart damage and accelerates cardiovascular disease. Published in PMC.

Treatment of cocaine cardiovascular toxicity: a systematic review

Richards et al. 2016 systematic review of emergency treatment for cocaine-induced tachycardia, hypertension, coronary vasospasm, and acute coronary syndrome. Benzodiazepines remain first-line; beta-blockers are controversial.

Neurotoxicity of crack cocaine exposure: evidence from a systematic review of in vitro and in vivo studies

2024 systematic review finding crack cocaine exposure causes neuroteratogenic effects, decreased seizure threshold, schizophrenic-like symptoms, and cognitive deficits beyond those of powder cocaine.

Cocaine, cardiomyopathy, and heart failure: a systematic review and meta-analysis

2020 Nature Scientific Reports meta-analysis revealing chronic cocaine use is associated with diastolic heart failure rather than the commonly taught dilated cardiomyopathy, challenging standard clinical assumptions.

Cocaine Toxicity

StatPearls (continuously updated) comprehensive clinical review covering cocaine pharmacology, toxicokinetics, clinical presentation of toxicity, and evidence-based emergency management protocols.

Neurotoxic and cardiotoxic effects of cocaine and ethanol

Pereira et al. 2015 study on cocaethylene — the toxic metabolite formed when cocaine and alcohol are co-ingested — which potentiates both cardiac and neurological toxicity beyond either substance alone.

Alprazolam 6 compound profile →

Benzodiazepine co-dependence exacerbates the opiate withdrawal syndrome

Brands et al. 2008 naturalistic study — first to examine clinical impact of benzodiazepine co-dependence on opiate withdrawal. Co-dependent patients had more severe withdrawal and lower detoxification completion rates.

Exposure-Response Association Between Concurrent Opioid and Benzodiazepine Use and Risk of Opioid-Related Overdose

Sun et al. 2017 study of Medicare beneficiaries showing concurrent benzodiazepine use is associated with a 5-fold increase in opioid-related overdose risk during the first 90 days. Published in JAMA Network Open.

The epidemiology of benzodiazepine misuse: A systematic review

Votaw et al. 2019 systematic review documenting that benzodiazepines are involved in nearly 30% of opioid overdose deaths. Maps global prevalence of misuse and identifies key risk populations.

Benzodiazepine Use Among Individuals with Opioid Use Disorder: A Narrative Review

2025 narrative review examining how benzodiazepines potentiate respiratory depression through complex drug interactions and hepatic dysfunction, producing increased opioid serum concentrations and exacerbating overdose risk.

Association between benzodiazepine and opioid prescription and mortality among patients in a large healthcare system

2022 large-scale healthcare system study demonstrating that concurrent benzodiazepine and opioid prescriptions significantly increase all-cause mortality, with dose-dependent risk escalation.

Benzodiazepine Co-Exposure Among Patients Presenting to the Emergency Department With a Confirmed Opioid Overdose

2025 ED study finding nearly one-third of confirmed opioid overdose patients had concomitant benzodiazepine exposure. Patients with novel benzodiazepines had significantly higher odds of requiring intubation.

Sananga 6 compound profile →

Extraction and Conversion Studies of the Antiaddictive Alkaloids Coronaridine, Ibogamine, Voacangine, and Ibogaine from Two Mexican Tabernaemontana Species

Krengel et al. 2019, Chemistry & Biodiversity. Characterizes the iboga-type indole alkaloids (coronaridine, ibogamine, voacangine, ibogaine) found across Tabernaemontana - the genus Sananga is made from.

Evaluation of the leishmanicidal activity of plants used by the Peruvian Chayahuita ethnic group

Estevez et al. 2007, Journal of Ethnopharmacology. Tabernaemontana sananho (a Sananga source species) showed good in-vitro activity against Leishmania - an anti-parasite finding, not an eye study.

Phytochemical Analysis by HPLC-HRESI-MS and Anti-Inflammatory Activity of Tabernaemontana catharinensis

Marques et al. 2018, International Journal of Molecular Sciences. Tabernaemontana catharinensis extract reduced paw edema and pro-inflammatory cytokines in animal models; illustrates genus bioactivity, not ocular use.

Use of Traditional Eye Medicines by corneal ulcer patients presenting to a hospital in South India

Prajna 1999, Indian Journal of Ophthalmology. ~48% of corneal-ulcer patients had used traditional eye remedies - the safety context for putting non-sterile substances like Sananga on the eye.

Traditional eye medicine use in microbial keratitis in Uganda: a mixed methods study

Arunga et al. 2019, Wellcome Open Research. Traditional-eye-medicine users presented later, with larger corneal ulcers and worse visual outcomes - directly relevant to Sananga's ocular risk.

Coronaridine, an iboga type alkaloid, inhibits the Wnt/beta-catenin signaling pathway

2015, example of preclinical bioactivity of coronaridine (a principal Sananga alkaloid). Lab activity of an isolated alkaloid - not evidence the eye drop is therapeutic.

Fentanyl 5 compound profile →

Overdose Deaths Involving Fentanyl and Fentanyl Analogs — New York City, 2000–2017

Colon-Berezin et al. 2019 CDC MMWR. Epidemiological analysis of fentanyl overdose deaths showing dramatic increase from 2 to 57% of overdose deaths.

Testing the test strips: laboratory performance of fentanyl test strips

Halifax et al. 2024 Harm Reduction Journal. Laboratory evaluation of fentanyl test strip accuracy for harm reduction applications.

Overdose Deaths with Carfentanil and Other Fentanyl Analogs Detected — 10 States, July 2016–June 2017

O'Donnell et al. 2018 CDC MMWR. Epidemiological report on carfentanil-involved overdose deaths across 10 states, documenting lethal doses and forensic findings.

Fentanyl Overdose

Walter 2023 JAMA. Clinical overview of fentanyl overdose presentation, treatment with naloxone, and harm reduction strategies.

Association of Law Enforcement Seizures of Heroin, Fentanyl, and Carfentanil With Opioid Overdose Deaths in Ohio, 2014-2017

Zibbell et al. 2019 JAMA Network Open. Analysis correlating carfentanil/fentanyl seizures with overdose mortality, establishing dose-lethality relationships.

Salvia 5

Salvinorin A, a kappa-opioid receptor agonist hallucinogen: pharmacology and potential template for novel pharmacotherapeutic agents in neuropsychiatric disorders

Butelman, Kreek 2015 Frontiers in Pharmacology. Comprehensive review of salvinorin A pharmacology as a selective kappa-opioid agonist and potential therapeutic applications.

Pharmacokinetics and Pharmacodynamics of Salvinorin A and Salvia divinorum: Clinical and Forensic Aspects

Brito-da-Costa et al. 2021 Pharmaceuticals. Review of salvinorin A pharmacokinetics, metabolism, and clinical implications for forensic assessment.

Salvinorin A and Salvia divinorum: Toxicology, Pharmacological Profile, and Therapeutic Potential

Calado et al. 2025 Int J Mol Sci. Comprehensive toxicology review covering salvinorin A safety profile, LD50 data, adverse effects, and therapeutic potential.

Solving an Old Puzzle: Elucidation and Evaluation of the Binding Mode of Salvinorin A at the Kappa Opioid Receptor

Puls & Wolber 2023 Molecules. Computational study elucidating salvinorin A's unique binding mode at kappa opioid receptor, explaining its selective agonism.

A review of salvinorin analogs and their kappa-opioid receptor activity

Roach & Shenvi 2018 Bioorg Med Chem Lett. Review of salvinorin A analogs and structure-activity relationships for kappa opioid receptor binding.

Methamphetamine 5 compound profile →

Methamphetamine-Induced Neuronal Damage: Neurotoxicity and Neuroinflammation

Jayanthi et al. 2021 review of METH-induced neurotoxicity mechanisms including oxidative stress, mitochondrial dysfunction, dopamine/serotonin terminal degeneration, and neuroinflammation via microglial activation. Published in PMC.

Molecular, Behavioral, and Physiological Consequences of Methamphetamine Neurotoxicity: Implications for Treatment

Moszczynska & Callan 2017 comprehensive review covering METH's effects on striatum, prefrontal cortex, and hippocampus. MRI/PET imaging shows structural brain changes in chronic users. No FDA-approved therapy exists for METH neurotoxicity.

Methamphetamine Neurotoxicity: Neurotoxic Effects, Mechanism of Toxicity, Molecular Mechanisms and Treatment Strategies

2024 review of METH neurotoxic effects including attention deficit, memory loss, and cognitive decline mediated through oxidative stress, excitotoxicity, DNA damage, and apoptosis pathways.

Methamphetamine induced neurotoxic diseases, molecular mechanism, and current treatment strategies

Meftahi et al. 2022 review of METH-induced Parkinson's-like symptoms, psychosis, and cognitive disorders. Covers experimental treatment strategies targeting oxidative stress, neuroinflammation, and mitochondrial impairment.

Chronic Methamphetamine Effects on Brain Structure and Function in Rats

Kesby et al. 2016 preclinical study demonstrating chronic METH exposure causes persistent structural brain changes including reduced prefrontal cortex volume and impaired cognitive flexibility, even after extended abstinence.

Kanna 4 compound profile →

Sceletium tortuosum effects on anxiety: A systematic review and meta-analysis

Gouhie et al. 2023 Brain Disorders. Meta-analysis examining Kanna's anxiolytic effects across multiple studies, finding significant anxiety reduction.

Sceletium tortuosum: A review on its phytochemistry, pharmacokinetics, biological, pre-clinical and clinical activities

Olatunji et al. 2022 J Ethnopharmacology. Comprehensive review of Kanna's chemistry, pharmacology, and clinical evidence for anxiety and cognitive effects.

First toxicity profile prediction for mesembrine – archetypal psychoactive Sceletium alkaloid

Niżnik, Jurowski 2025 Chemico-Biological Interactions. First computational toxicity prediction for kanna's main alkaloid mesembrine, predicting LD50 and key toxicological endpoints.

A Chewable Cure 'Kanna': Biological and Pharmaceutical Properties of Sceletium tortuosum

Manganyi et al. 2021 Molecules. Review of kanna biological activities, safety profile, and pharmaceutical potential including toxicity considerations.

Caffeine 4 compound profile →

Coffee and caffeine consumption and depression: A meta-analysis of observational studies

Wang et al. 2016 Aust NZ J Psychiatry. Meta-analysis of 11 studies showing coffee/caffeine consumption associated with decreased depression risk.

Caffeine Consumption Patterns, Health Impacts, and Media Influence: A Narrative Review

2025 comprehensive review covering caffeine's cognitive benefits, physical performance enhancement, cardiovascular risks, addiction potential, and sleep disruption. Documents individual variability in caffeine metabolism due to CYP1A2 genetics.

The effect of caffeine on subsequent sleep: A systematic review and meta-analysis

Gardiner et al. 2023 meta-analysis finding caffeine reduces total sleep time by 45 minutes, increases sleep onset latency, and reduces sleep efficiency. Effects persist up to 8+ hours due to caffeine's variable half-life across individuals.

Dose and timing effects of caffeine on subsequent sleep: a randomized clinical crossover trial

2024 randomized clinical crossover trial published in SLEEP demonstrating dose-dependent and timing-dependent caffeine effects on polysomnographic sleep measures. Consumption at 3pm reduced sleep more than at 9am.

Heroin 4 compound profile →

The Changing Opioid Crisis: development, challenges and opportunities

Volkow & Blanco 2021 comprehensive review of the four waves of opioid overdose deaths: prescription opioids, heroin, synthetic opioids, and polysubstance use. Covers neurobiology of addiction and promising harm reduction strategies.

Effectiveness of naloxone distribution in community settings to reduce opioid overdose deaths: a systematic review and meta-analysis

2025 systematic review and meta-analysis demonstrating lifesaving effects of community-based naloxone distribution programs. Warrants substantial expansion in nearly every US state.

Estimating naloxone need in the USA across fentanyl, heroin, and prescription opioid epidemics

Irvine et al. 2022 Lancet modelling study estimating naloxone distribution needs across different opioid epidemic phases. Fentanyl overdoses are harder to reverse than heroin overdoses, requiring higher naloxone doses.

Fentanyl-Plus: A New Era of Fentanyl Polydrug Combinations in the North American Overdose Crisis

Ciccarone 2025 review of the 'fentanyl-plus' era where polysubstance combinations (fentanyl + xylazine, fentanyl + stimulants) define the current overdose crisis. Examines epidemiology, economics, and evolving harm reduction strategies.

Mescaline 3 compound profile →

Pharmacokinetic and Pharmacodynamic Aspects of Peyote and Mescaline: Clinical and Forensic Repercussions

Dinis-Oliveira et al. 2019 Current Molecular Pharmacology. Comprehensive review of mescaline/peyote pharmacokinetics, metabolism, and clinical implications.

An Overview on the Hallucinogenic Peyote and Its Alkaloid Mescaline: The Importance of Context, Ceremony and Culture

2023 Molecules. Review examining mescaline pharmacology, traditional ceremonial use in Native American Church, and modern therapeutic potential.

Peyote and mescaline exposures: a 12-year review of a statewide poison center database

2010 Clinical Toxicology. Retrospective analysis of mescaline/peyote exposure reports documenting clinical presentation and outcomes.

2C-B 3 compound profile →

4-Bromo-2,5-dimethoxyphenethylamine (2C-B): presence in the recreational drug market in Spain, pattern of use and subjective effects

Caudevilla-Gálligo et al. 2012 J Psychopharmacology. Survey of 2C-B users (n=98) documenting patterns of use, subjective effects, and market presence in Spain.

Behavioral, neurochemical and pharmaco-EEG profiles of the psychedelic drug 4-bromo-2,5-dimethoxyphenethylamine (2C-B) in rats

Páleníček et al. 2013 Psychopharmacology. Preclinical study characterizing 2C-B pharmacology, serotonin release, and EEG changes compared to other psychedelics.

The Clinical Toxicology of 4-Bromo-2,5-dimethoxyphenethylamine (2C-B): The Severity of Poisoning After Analytically Confirmed Use

2020 Annals of Emergency Medicine. Clinical case series examining 2C-B toxicity presentations and outcomes in analytically confirmed cases.

Placebo 2

Blinding and expectancy confounds in psychedelic randomized controlled trials

Muthukumaraswamy et al. 2021 Expert Review of Clinical Pharmacology. Analysis of blinding challenges in psychedelic trials and implications for interpreting treatment effects.

Expectancy Effects, Failure of Blinding Integrity, and Placebo Response in Trials of Treatments for Psychiatric Disorders

Huneke et al. 2025 JAMA Psychiatry. Analysis of expectancy effects and blinding failures across psychiatric treatment trials including psychedelics.