Psilocybin for Cancer Pain
Recruiting in Palo Alto (17 mi)
+2 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Yvan Beaussant, MD, MSci
Must be taking: Opioids
Must not be taking: Antidepressants, Antipsychotics, Mood stabilizers, others
Disqualifiers: Psychotic disorder, Bipolar, Heart disease, others
No Placebo Group
Prior Safety Data
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?The overall objective of this study is to assess the feasibility, safety and preliminary efficacy of psilocybin-assisted therapy to alleviate opioid-refractory pain in patients with advanced-cancer.
The name of the study intervention used in this research study is:
Psilocybin (a tryptamine derivative)
Will I have to stop taking my current medications?
The trial requires participants to stop taking certain medications that could interact with psilocybin, such as antidepressants, antipsychotics, and mood stabilizers. These medications will need to be tapered off appropriately to avoid withdrawal effects before participating in the study.
What data supports the effectiveness of the drug psilocybin for cancer pain?
Research suggests that psilocybin may have therapeutic benefits in palliative care, which often includes managing cancer pain, although it is not yet approved for this use in the U.S. Additionally, psilocybin has shown potential in treating major depressive disorder, which can be relevant as depression often accompanies chronic pain conditions.
12345Is psilocybin safe for human use?
Psilocybin is generally considered safe when used in controlled settings with proper screening and support, although it can cause challenging psychological experiences and, in rare cases, lead to risky behavior or enduring psychological distress. It is important to use it under medical supervision, especially for individuals with pre-existing mental health conditions.
26789How does the drug psilocybin differ from other treatments for cancer pain?
Psilocybin is unique because it is a psychoactive compound found in certain mushrooms, known for its hallucinogenic effects, and is being explored for its potential to alleviate cancer pain by affecting the brain's perception of pain. Unlike traditional pain medications, psilocybin may offer a novel approach by potentially altering consciousness and emotional responses to pain.
24101112Eligibility Criteria
Adults with advanced cancer experiencing pain not relieved by opioids, on a high opioid dose, and seen by palliative care recently. They must be able to take pills, consent to the study, have certain organ functions within safe ranges, and commit to lifestyle changes for the trial. Pregnant women or those who can become pregnant without effective birth control are excluded.Inclusion Criteria
I can take care of myself and am up and about more than 50% of my waking hours.
My cancer is advanced and not likely to be cured.
I am 18 years old or older.
+10 more
Exclusion Criteria
I am not on any medications that can't be stopped and would interfere with the study drugs.
I have risk factors for a specific heart rhythm condition (like heart failure or low potassium).
Participants with a history of, or a current diagnostic of primary psychotic disorder, major depressive disorder with psychotic features, bipolar affective disorder type 1 or history of or current dissociative identity disorder; and participants who have an ongoing substance use disorder (defined as active in the past year). Participants with first-degree relatives with schizophrenia or bipolar disorder may be eligible depending on their age and personal and family psychiatric history. The decision will be made by the principal investigator and study psychiatrist based on risk assessment
+17 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
1 visit (in-person)
Preparation
Participants undergo 2 preparation sessions with therapists, either in-clinic or remote
1-2 weeks
2 visits (in-person or remote)
Treatment
Participants receive a single psilocybin session in-clinic with therapists
1 day
1 visit (in-person)
Integration
Participants have integration sessions with therapists, including one the day after treatment and another one week later
1 week
2 visits (in-person or remote)
Follow-up
Participants are monitored for safety and effectiveness after treatment with follow-up visits at weeks 2, 3, 5, 8, and 12
12 weeks
5 visits (in-person or remote)
Participant Groups
The trial is testing psilocybin-assisted therapy's safety and ability to reduce pain in patients with advanced cancer whose pain isn't managed by opioids. Participants will receive doses of psilocybin under controlled conditions.
1Treatment groups
Experimental Treatment
Group I: PsilocybinExperimental Treatment1 Intervention
Participants will complete study procedures as follows:
* 2, in-clinic or remote, preparation sessions with therapists.
* In-clinic treatment session with therapists at Dana-Farber Cancer Institute. Participants will take a predetermined amount of psilocybin once. Participants will be transported home by a friend or family member.
* In-clinic integration session the day after psilocybin administration with therapists.
* In-clinic or remote, integration session with therapists 1 week after psilocybin administration.
* In-clinic or remote follow visits with therapists at week 2, 3, 5, 8, and 12 after psilocybin administration.
Psilocybin is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Psilocybin for:
- Treatment-resistant depression (TRD) under Breakthrough Therapy designation
🇪🇺 Approved in European Union as Psilocybin for:
- Treatment-resistant depression (TRD) under PRIME designation
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Brigham and Women's HospitalBoston, MA
Dana-Farber Cancer InstituteBoston, MA
Massachusetts General HospitalBoston, MA
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Who Is Running the Clinical Trial?
Yvan Beaussant, MD, MSciLead Sponsor
Cy BiopharmaCollaborator
Pancreatic Cancer North AmericaCollaborator
References
Psilocybin in Palliative Care: An Update. [2023]This review article summarizes clinically and socially relevant developments over the past five years in the therapeutic use of the classical tryptamine psychedelic substance psilocybin, with respect to the common challenges faced by palliative care patients and their care teams. Psilocybin is available in whole fungal and isolated forms but is not yet approved for therapeutic use in the United States. Using targeted database and gray literature searches, and author recall, key sources were identified, reviewed, and synthesized as to the safety and efficacy of psilocybin in palliative care.
The pharmacology of psilocybin. [2016]Psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine) is the major psychoactive alkaloid of some species of mushrooms distributed worldwide. These mushrooms represent a growing problem regarding hallucinogenic drug abuse. Despite its experimental medical use in the 1960s, only very few pharmacological data about psilocybin were known until recently. Because of its still growing capacity for abuse and the widely dispersed data this review presents all the available pharmacological data about psilocybin.
Brain serotonin 2A receptor binding predicts subjective temporal and mystical effects of psilocybin in healthy humans. [2022]Psilocybin is a serotonergic psychedelic with psychoactive effects mediated by serotonin 2A receptor (5-HT2AR) activation. It produces an acute psychedelic altered state of consciousness with a unique phenomenology that can be temporally characterized by three intensity phases: onset of psychoactive effect, a peak plateau and return to normal consciousness.
Therapeutic Effects of Medicinal Mushrooms on Gastric, Breast, and Colorectal Cancer: A Scoping Review. [2023]Cancer is the leading cause of mortality globally. With anticancer medications causing severe adverse effects, understanding the role of alternative and efficacious anticancer treatments with minimal or no side effects can be beneficial. Edible mushrooms have been associated with certain health benefits and exhibit a broad range of pharmacological activities, including anti-inflammatory and immunomodulating activities. The anticancer potential of different mushrooms is now being tested. The goal of this scoping review was to discuss the most recent and available evidence on the therapeutic uses of medicinal mushrooms in cancer treatment, specifically those cancers with some of the highest mortality rates (i.e., gastric, breast, and colorectal cancer). Randomly controlled trials, clinical trials, and retrospective cohort studies (with placebo group) with human subjects published between 2012-2023 were searched using the databases Embase, Ovid MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINHAL), and Alt HealthWatch. The initial search yielded 2,202 articles. After removing 853 duplicate citations, 1,349 articles remained and were screened for study eligibility and accessibility, leaving 26 articles. The inclusion and exclusion criteria were then used to assess the remaining 26 full-text articles and nine articles were selected for the final review. The characteristics of the nine studies reported the efficacy of medicinal mushrooms Lentinus edodes (Shiitake), Coriolus versicolor (Turkey Tail), and Agaricus Sylvaticus (Scaly Wood), in treating symptoms, medication side effects, anti-tumor effects, and survival outcomes in gastric, breast, and colorectal cancers. Findings from this review suggest that medicinal mushrooms have the potential to prevent lymph node metastasis, prolong overall survival, decrease chemotherapy-induced side effects (e.g., diarrhea, vomiting), affect the immune system, and help maintain immune function and quality of life in patients with certain cancers. More research is needed with human subjects using RCTs with larger samples to ensure accurate outcomes and ascertain the most efficacious dosages.
Efficacy and safety of psilocybin-assisted treatment for major depressive disorder: Prospective 12-month follow-up. [2022]Preliminary data suggest that psilocybin-assisted treatment produces substantial and rapid antidepressant effects in patients with major depressive disorder (MDD), but little is known about long-term outcomes.
Effects and safety of Psilocybe cubensis and Panaeolus cyanescens magic mushroom extracts on endothelin-1-induced hypertrophy and cell injury in cardiomyocytes. [2021]Prevalence of major depression in people with chronic heart failure is higher than in normal populations. Depression in heart failure has become a major issue. Psilocybin-containing mushrooms commonly known as magic mushrooms, have been used since ancient times for their mind healing properties. Their safety in cardiovascular disease conditions is not fully known and may pose as a risk for users suffering from these illnesses. Study investigates the effects and safety of Psilocybe cubensis and Panaeolus cyanescens magic mushrooms use from genus Psilocybe and Panaeolus respectively, in a pathological hypertrophy conditions in which endothelin-1 disorder is a contributor to pathogenesis. We examined the effects of the mushrooms extracts on endothelin-1-induced hypertrophy and tumor necrosis factor-α (TNF- α)-induced cell injury in H9C2 cardiomyocytes. Mushrooms were oven dried and extracted with cold and boiling-hot water. H9C2 cardiomyocytes were induced with endothelin-1 prior to treatment with extracts over 48 h. Cell injury was stimulated with TNF-α. Results proposed that the water extracts of Panaeolus cyanescens and Psilocybe cubensis did not aggravate the pathological hypertrophy induced by endothelin-1 and also protected against the TNF-α-induced injury and cell death in concentrations used. Results support medicinal safe use of mushrooms under controlled conditions and cautioned use of higher concentrations.
Survey study of challenging experiences after ingesting psilocybin mushrooms: Acute and enduring positive and negative consequences. [2018]Acute and enduring adverse effects of psilocybin have been reported anecdotally, but have not been well characterized. For this study, 1993 individuals (mean age 30 yrs; 78% male) completed an online survey about their single most psychologically difficult or challenging experience (worst "bad trip") after consuming psilocybin mushrooms. Thirty-nine percent rated it among the top five most challenging experiences of his/her lifetime. Eleven percent put self or others at risk of physical harm; factors increasing the likelihood of risk included estimated dose, duration and difficulty of the experience, and absence of physical comfort and social support. Of the respondents, 2.6% behaved in a physically aggressive or violent manner and 2.7% received medical help. Of those whose experience occurred >1 year before, 7.6% sought treatment for enduring psychological symptoms. Three cases appeared associated with onset of enduring psychotic symptoms and three cases with attempted suicide. Multiple regression analysis showed degree of difficulty was positively associated, and duration was negatively associated, with enduring increases in well-being. Difficulty of experience was positively associated with dose. Despite difficulties, 84% endorsed benefiting from the experience. The incidence of risky behavior or enduring psychological distress is extremely low when psilocybin is given in laboratory studies to screened, prepared, and supported participants.
[Hallucinogenic mushrooms]. [2018]The group of hallucinogenic mushrooms (species of the genera Conocybe, Gymnopilus, Panaeolus, Pluteus, Psilocybe, and Stropharia) is psilocybin-containing mushrooms. These "magic", psychoactive fungi have the serotonergic hallucinogen psilocybin. Toxicity of these mushrooms is substantial because of the popularity of hallucinogens. Psilocybin and its active metabolite psilocin are similar to lysergic acid diethylamide. These hallucinogens affect the central nervous system rapidly (within 0.5-1 hour after ingestion), producing ataxia, hyperkinesis, and hallucinations. In this review article there are discussed about history of use of hallucinogenic mushrooms and epidemiology; pharmacology, pharmacodynamics, somatic effects and pharmacokinetics of psilocybin, the clinical effects of psilocybin and psilocin, signs and symptoms of ingestion of hallucinogenic mushrooms, treatment and prognosis.
Intravenous mushroom poisoning. [2019]Mushrooms of the genus Psilocybe frequently are ingested by recreational drug users for their hallucinogenic effects. We present the case of a 30-year-old man who allegedly received an intravenous injection of an extract of Psilocybe mushrooms. His clinical course was characterized in part by vomiting, severe myalgias, hyperpyrexia, hypoxemia, and mild methemoglobinemia, and it was similar to two previously reported cases. The patient improved rapidly with supportive care.
Magic truffles or Philosopher's stones: a legal way to sell psilocybin? [2019]"Magic mushrooms" is the most common name given to hallucinogenic fungi containing the psychoactive alkaloids psilocybin and psilocin. In recent years, fungis' sclerotia, commonly called "magic truffles" have become a form of supply of psychoactive Psilocybe alkaloids since Psilocybe sclerotia are not specifically included in the laws banning the sale, the purchase and the use of such substances and mushrooms containing them. A liquid chromatography -tandem mass spectrometry (LC-MS/MS) method was developed for the rapid determination of psilocybin and psilocin in Psilocybe sclerotia. Following a simple step extraction with methanol, the alkaloids were separated on a reversed-phase column using a gradient of 0.1% formic acid - acetonitrile s a mobile phase at a flow rate of 0.2 mL/min.. Separated analytes were detected by electrospray ionization tandem mass spectrometry in the positive ion mode using multiple reaction monitoring. The developed method was linear over the calibration range for all two substances under investigation, with a r(2) > 0.99. The detection and quantification limits were 0.3 µg and 1 µg per 100 mg truffles, for both psilocin and psilocybin and the intra- and inter-day coefficients of variation were always better than 15%. Using this method, the presence of only psilocybin was demonstrated in examined Psilocybe sclerotia. The content of psilocybin was found to vary over a concentration range of 59.3 to 167.8 µg per 100 mg of fresh sclerotia.
Apoptosis and Anti-cancer Drug Discovery: The Power of Medicinal Fungi and Plants. [2021]The purpose of this account is to review the compounds capable of eliciting mitochondria-mediated apoptosis in cancer cells produced by medicinal fungi and plants. The medicinal fungi discussed encompass Cordyceps, Ganoderma species, Coriolus versicolor and Hypsizygus marmoreus. The medicinal plants discussed comprise Astragalus complanatus, Dendrobium spp, Dioscorea spp, Glycyrrhiza spp, Panax notoginseng, Panax ginseng, and Momordica charantia. These compounds have the potential of development into anticancer drugs.
Genetic Survey of Psilocybe Natural Products. [2022]Psilocybe magic mushrooms are best known for their main natural product, psilocybin, and its dephosphorylated congener, the psychedelic metabolite psilocin. Beyond tryptamines, the secondary metabolome of these fungi is poorly understood. The genomes of five species (P. azurescens, P. cubensis, P. cyanescens, P. mexicana, and P. serbica) were browsed to understand more profoundly common and species-specific metabolic capacities. The genomic analyses revealed a much greater and yet unexplored metabolic diversity than evident from parallel chemical analyses. P. cyanescens and P. mexicana were identified as aeruginascin producers. Lumichrome and verpacamide A were also detected as Psilocybe metabolites. The observations concerning the potential secondary metabolome of this fungal genus support pharmacological and toxicological efforts to find a rational basis for yet elusive phenomena, such as paralytic effects, attributed to consumption of some magic mushrooms.