SUBSTANCE BRIEF
Psychedelics are a class of natural and synthetic compounds that manifest the mind. Users report feelings of a transcendence of space and time, unity, sacredness, and a dissolution of the ego. Experiences vary widely based on the individual and the type of substance used; some even report mystical experiences cultivating creativity and productivity, while others describe negative feelings or fashbacks in what is coined a “bad trip.”38 Further, use has also been described as an entheogen or spiritual experience. While their MOA is not fully understood, psychedelics’ primary efect and target is that of an agonist or partial agonist at the brain’s serotonin 5-HT2A receptors. They also have actions at other serotonin receptors such as 5-HT1A and 5-HT2C receptors where they have agonist or partial agonist activity. While not designated as classical psychedelics, ketamine and esketamine are postulated to exhibit their antidepressant efects through modulation of the neurotransmitter glutamate and N-methyl-D-aspartate (NMDA) receptor antagonism.39 More research is needed to confrm if the hallucinogenic and dissociative efects seen with these agents are due to the same mechanism. Although selective serotonin reuptake inhibitors (SSRIs) and psychedelics share some similarities, it is hypothesized that psychedelics work diferently than SSRIs, activating serotonin receptors in a way that creates an emotional release or “reset” in the brain’s processes and leading to longer lasting remission of depressive symptoms that can last weeks or months after one psychedelic treatment in contrast to taking daily antidepressants.40 While marijuana and NMDA products can be addictive, psychedelics have largely not demonstrated to lead to addiction or dependence as they do not induce cravings or an impulse to re-dose once the desired efects have waned. This may be due to the primarily serotonergic properties without a direct efect on the brain’s dopamine receptors.41
Psilocybin
Psilocybin, known as “magic mushrooms” is a psychoactive prodrug of the Psilocybe genus, dating back thousands of years. When ingested, it converts to the active ingredient psilocin, which causes a psychedelic response similar to LSD and mescaline (a hallucinogen derived from the Peyote cactus primarily used in religious rituals).42, 43, 44 Psilocybin has been granted “Breakthrough Therapy” designation by the FDA for TRD and is currently in phase 2 trials for this use. The current hypothesis is psilocybin is safe and efective when administered in a “controlled setting.”45, 46
• MOA: Psilocybin is actively metabolized to psilocin, a serotonin transporter inhibitor and 5-HT2A receptor partial agonist. Binding sites also include 5-HT2C , 5-HT1A , and 5-HT1B receptors, with binding afnities in descending order.
• Addictive properties: Researchers at Johns Hopkins University evaluated the abuse potential of medically administered psilocybin and determined that it would be appropriate for a schedule IV classifcation.47
MDMA
3,4-Methylenedioxymethamphetamine (MDMA), also known as ecstasy or molly, is a synthetic member of the phenylethtlamine drug class. Phenylethylamines naturally occur in mescaline/ peyote. MDMA has been granted FDA’s Breakthrough Therapy designation and is currently in phase 3 trials to evaluate the efcacy of treatment for PTSD, addiction, anorexia, and autism.
• MOA: The efects of MDMA are believed to be mediated by a number of mechanisms, including monoamine release, serotonin and norepinephrine transporter reuptake inhibition, monoamine oxidase inhibition, partial agonism of serotonin receptors (5-HT2A , 5-HT1A , and 5-HT2C receptors).48
• Addictive Properties: In a recent phase 3 clinical trial MDMA was not shown to induce or potentiate abuse potential.
LSD
Lysergic acid diethylamide (LSD) is described as a classical hallucinogen. It is synthetically made from lysergic acid found in a fungus called ergot that grows on grains.49 Its psychosensory effects are primarily mediated by the activation of specifc sensors in the brain. LSD is an odorless and colorless substance with a slightly bitter taste.50
• MOA: The mechanism by which LSD works is mainly mediated by activation of serotonin receptors (namely 5-HT2A receptors or 5-HT2AR) with modulation of the 5-HT2C and 5-HT1A receptors. The interactions between the receptor activation and the resulting impairment in cognition and induction of hallucinations are still poorly understood.51
• Addictive Properties: Psychological and physiological tolerance has been reported after repeated daily administration of 3 to 7 days. It has not been observed in studies to produce dependence or reinforcing efects. LSD may be misused but has not demonstrated addictive properties.52, 53, 54, 55
Cannabis
Cannabis is not classifed as a psychedelic, yet it does not ft neatly into one category. The cannabis Sativa plant, also known as marijuana, has several chemotypes. Cannabinoids are a group of substances found in cannabis. Over 100 cannabinoid compounds have been found in cannabis. The main cannabinoids are delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD).56 THC is the main psychoactive substance in marijuana, therefore some of cannabis’ efects are psychedelic in nature and relevant to the psychedelic landscape.57 CBD is the active ingredient in oral cannabidiol (Epidiolex®), which is FDA-approved for select seizures. CBD is a marijuana derivative; however, it lacks the psychoactive properties commonly associated with THC.
• MOA: Cannabis, commonly known as marijuana, is thought to exert its pharmacologic activity via several mechanisms; the frst and most studied is a receptor-mediated MOA.58
• Addictive Properties: Physiological dependence may occur in patients on long-term marijuana treatment.
Ketamine
Ketamine is a dissociative anesthetic that has some hallucinogenic efects. Since the 1970’s, ketamine has been marketed in the US as an injectable, short-acting anesthetic for use in humans and animals. It is approved by the US Food and Drug Administration (FDA) for general anesthesia and procedural sedation.
• MOA: Ketamine’s analgesic and anesthetic efects are a result of N-methyl-D-aspartate (NMDA) receptor antagonism (which blocks the excitatory neurotransmitter glutamate) as well as interaction with opioid and cholinergic transmission. Ketamine selectively interrupts association pathways of the brain before producing somatesthetic sensory blockade; ‘dissociative anesthesia’ is induced through inhibition of thalamoneocortical pathways and limbic stimulation. Functional and electrophysiological dissociation between the cortical and limbic systems prevents higher centers from perceiving visual, auditory, or painful stimuli.59
• Addictive Properties: Abuse and misuse have been reported. Recurrent high doses may be tied to memory and/or attention impairment. Individuals with a history of drug abuse or dependence may be at a greater risk. Physical dependence and tolerance have also been reported with prolonged use. Withdrawal symptoms have been reported after the discontinuation of extended and frequent large doses of ketamine.60
Esketamine (Spravato)
In 2019 the FDA approved the S(+) enantiomer of ketamine (esketamine) nasal spray (Spravato) for treatment-resistant depression (TRD) and subsequently to treat depressive symptoms in adults with MDD with acute suicidal ideation or behavior. It is self-administered under HCP supervision and only available at a certifed doctor’s ofce or clinic.
• MOA: Esketamine non-selectively blocks the NMDA receptor, which is an ionotropic glutamate receptor. Esketamine is the S-enantiomer of ketamine, which is primarily used for its anesthetic properties. The mechanism by which esketamine exerts its antidepressant efect is unknown; however, the activity on NMDA receptors may be responsible for both the therapeutic and the adverse psychiatric efects of esketamine, including dissociative symptoms and abuse.61
• Addictive Properties: There is a risk for abuse, misuse, and physiological and psychological dependence. Due to the aforementioned and the risks for sedation and dissociation, esketamine is only available through the FDA Risk Evaluation and Mitigation (REMS) program.62
SITE OF CARE
As psychedelic-assisted psychotherapy becomes better supported by scientifc research, treatment centers are now available in the US. The majority of of-label ketamine treatments are performed in an ofce or psychedelic-centered treatment settings. This might serve as a model for clinical therapeutic regulatory requirements if psychedelics are approved. Field Trip Health Centers have treatment programs in the US and overseas ofering therapist-guided one-on-one or group ketamine sessions.63 Multiple other treatment centers in diferent states also provide ketamine-assisted psychotherapy and one even provides treatment in the home setting.
Mindbloom is an example of a mental health and wellbeing company that partners with clinicians, technologists, and researchers to increase access to science-backed psychedelic medicine treatments. Their team facilitates ketamine-assisted therapy through an online assessment and video consultation before arriving at the patient’s home for a clinician-guided treatment session.64 Psychedelic-assisted psychotherapy follows a traditional framework adhering to the idea of “set and setting.” Patients are to be properly screened, prepared and monitored during sessions. Sessions include elements such as soft lighting, patient-selected music, comfortable or natural surroundings, and compassionate, skilled guides to help facilitate the journey.65 With the growth of telehealth spurred by the pandemic, the burgeoning development of artifcial intelligence and wearables, and as diferent dosage forms and modes of delivery are investigated, the long-term outlook for psychedelic site of care is evolving.
CLINICAL TRIAL EVIDENCE
While there are many clinical trials for psychedelics, currently there is a lack of high-quality published studies in the literature; most are in earlier phases of study, open-label or single-blind design, with small numbers of participants. A limited number of randomized controlled clinical trials have recently been conducted for psychedelics and other psychoactive substances such as cannabis and ketamines. A literature search was performed for the aforementioned psychedelics, cannabis, and ketamines. Studies considered most relevant for the analysis included US, phase 3, randomized, controlled trials, published in English with a behavioral health diagnosis. These high-quality studies are summarized below. This is not an all-inclusive list.
A small trial that did not meet inclusion criteria (as it was in an earlier phase [phase 2] study), but warrants mention, is the widely discussed study, “Trial of psilocybin versus escitalopram for depression,” published in The New England Journal of Medicine. 66 While the change in depression scores did not difer signifcantly between the two groups, this trial is notable because it compared a psychedelic (psilocybin) to a traditional standard of care (escitalopram) in a randomized, controlled trial in patients with moderate to severe MDD.
AUTHOR TRIAL DESIGN OBJECTIVE
MDMA
Mitchell JM, et al 2021
Phase 3, randomized, double-blind, placebocontrolled, multicenter
To compare the efcacy and safety of MDMAassisted therapy or placebo with therapy in patients with severe PTSD
NUMBER OF PARTICIPANTS
90
INTERVENTION, FORMULATION & PRIMARY ENDPOINT
Modifed intent-totreat randomized & blinded, allocated 1:1 to either the MDMAassisted therapy group or the placebo with therapy group
Dosage form: compounded capsules
Primary Endpoint ClinicianAdministered PTSD Scale for DSM5(CAPS-5)
RESULTS
MDMA was found to attenuate CAPS5 score compared with placebo (p<0.0001, d=0.91)
MMRM analysis of the de jure estimand showed a signifcant diference in treatment arms (n=89 [MDMA n=46], p<0.0001, between-group diference=11.9, 95% CI=6.3 to 17.4, df=71)
MMRM sensitivity analysis of the de facto estimand showed a signifcant diference in treatment arms (n=90, p<0.0001, df=72)
ESKETAMINE
Fedgchin M, et al 2019
Daly EJ, et al 2019
Phase 3, randomized, double-blind, multicenter
Phase 3, randomized, double-blind, multicenter
Efcacy and safety of fxed dose esketamine nasal spray combined with a new oral antidepressant in patients with recurrent MDD
Assess the efcacy of esketamine nasal spray plus an oral antidepressant compared with an oral antidepressant plus placebo nasal spray in TRD
346 Randomized (1:1:1) to double-blind nasal spray treatment with either 1 of 2 fxed doses of esketamine (56 or 84 mg) or placebo
Dosage form: nasal spray
Primary Endpoint
Change from baseline to day 28 in the Montgomery-Asberg Depression Rating Scale total score
297 Randomized 1:1 to continue esketamine nasal spray or discontinue esketamine treatment and switch to placebo nasal spray, with oral antidepressant treatment continued
Dosage form: nasal spray
Primary Endpoint
Time to relapse was examined in patients who achieved stable remission
ADVERSE EVENTS & SAFETY CONCLUSION
No increase in AE related to suicidality was observed in the MDMA group. Five participants in the placebo group & 3 participants in the MDMA group reported AE of suicidal ideation, suicidal behavior or self-harm in the context of suicidal ideation. MDMA did not induce adverse events of abuse potential, suicidality or QT prolongation
MDMA-assisted therapy was efcacious in individuals with severe PTSD
Did not reach statistical signifcance with esketamine 84 mg/antidepressant compared with antidepressant/ placebo (least squares [LS] means diference [95% CI]: -3.2 [-6.88 to 0.45]; 2-sided p=0.088)
Safety was similar between esketamine or antidepressant groups and no new dose-related safety concerns were identifed
Esketamine 84 mg/ antidepressant was not statistically signifcant to placebo; therefore the esketamine 56 mg/ antidepressant arm was not evaluated
Continued treatment with esketamine and antidepressant signifcantly delayed relapse compared with treatment with antidepressant and placebo (patients who achieved stable remission: HR, 0.49; 95% CI, 0.29 to 0.84; p=0.003)
Most commonly reported; dysgeusia, vertigo, dissociation, somnolence, and dizziness and were transient in nature. No new or unexpected safety concern was observed
Continued treatment with esketamine past the initial treatment phase was clinically and statistically signifcant in preventing relapse
AUTHOR TRIAL DESIGN OBJECTIVE
ESKETAMINE continued
Ochs-Ross R, et al 2020
Fu, et al 2020
Phase 3, randomized, double-blind
In patients with TRD & ≥65 years, assess the efcacy and safety of esketamine nasal spray plus a newly initiated oral antidepressant as compared with a newly initiated oral antidepressant and placebo nasal spray
NUMBER OF PARTICIPANTS
INTERVENTION, FORMULATION & PRIMARY ENDPOINT
137
Phase 3, randomized, double-blind, multicenter
Compare esketamine to placebo, each in addition to standard-of-care treatment, for rapidly reducing MDD symptoms, including suicidal ideation
Patients were randomized to a new oral antidepressant and fexibly-dosed esketamine or placebo nasal spray
Dosage form: nasal spray
Primary Endpoint
Change in the MADRS from baseline to day 28
RESULTS
The median unbiased estimate of the diference (95% CI) between the esketamine/ antidepressant and the antidepressant/ placebo group was −3.6 (−7.20 to 0.07); weighted combination test (based on MMRM analyses) z=1.89, two-sided p=0.059
ADVERSE EVENTS & SAFETY CONCLUSION
The most common AE in the esketamine or antidepressant group were dizziness, nausea, elevated blood pressure. No suicide attempts or suicidal behavior were reported. (11.4%) patients in the esketamine or antidepressant and 9/65 (13.8%) in the antidepressant/ placebo group had post-baseline suicidal ideation; none had suicidal ideation at baseline
The results did not reach statistical signifcance. Adverse events in those over 65 years was similar to younger patients
Lonescu DF, et al 2021 Phase 3, randomized, double-blind, placebocontrolled, multicenter
Rapid reduction of depressive symptoms in patients with MDD who have active SI with intent
226 Randomized 1:1 to esketamine 84 mg or placebo nasal spray twice-weekly for 4 weeks
Dosage form: nasal spray
Primary Endpoint
Change from baseline to 24 hours post-frst change in MADRS total score
230 Randomized 1:1 to 84 mg esketamine nasal spray or matching placebo. Patients selfadministered intranasal drug twice weekly for 4 weeks
Dosage form: nasal spray
Primary Endpoint
Change from baseline to 24 hours post-frst dose in MADRS total score
Signifcantly greater improvement with MADRS total score decreased in both groups with greater improvement in esketamine cohort. (leastsquares mean diference [SE]: -3.8 [1.39]; 95% CI, −6.56 to −1.09; 2-sided p=0.006)
Greater improvement in MADRS total score was observed with esketamine (mean [SD]: -15.7 [11.56]) versus placebo (-12.4 [10.43]), (leastsquares mean diference [SE]: -3.9 [1.39], 95% CI: -6.60, -1.11; 2-sided p=0.006)
Most common were dizziness, dissociation, nausea, headache, increased blood pressure. One patient, treated with esketamine during the double-blind phase, died by suicide during the follow-up phase Esketamine nasal spray rapidly reduced depressive symptoms. Statistically and clinically signifcant results
Most common AE were dizziness, dissociation, nausea, dysgeusia, somnolence, headache, and paresthesia. No AE of psychosis were reported during treatment. Patients who reported AE potentially related to suicidality during the double-blind treatment phase were balanced between the treatment groups
Treatment with esketamine plus the standard of care led to signifcantly and clinically greater improvement
Dong-Jing
AUTHOR TRIAL DESIGN OBJECTIVE
ESKETAMINE continued
Popova V, et al 2019
Phase 3, randomized, double-blind, activecontrolled, multicenter
Compare the efcacy and safety of switching patients with TRD from an inefective antidepressant to fexibly dosed esketamine nasal spray plus a newly initiated antidepressant or to a newly initiated antidepressant plus placebo nasal spray
NUMBER OF PARTICIPANTS
INTERVENTION, FORMULATION & PRIMARY ENDPOINT
223 Confrmed nonresponders were randomly assigned to treatment with esketamine nasal spray (56 or 84 mg twice weekly) and an antidepressant or antidepressant and placebo nasal spray
Dosage form: nasal spray
Primary Endpoint
Change from baseline to day 28 in MADRS score
RESULTS ADVERSE EVENTS & SAFETY CONCLUSION
Greater improvement observed among those in the esketamine plus antidepressant arm as compared with the antidepressant plus placebo arm (diference of least square means=−4, SE=1.69, 95% CI=−7.31 to −0.64; p=0.020)
Most common AE were dizziness, dissociation, dysgeusia, vertigo, and nausea. Nine patients experienced one or more AE leading to discontinuation of intranasal study drug during the treatment phase, 7% in the esketamine plus antidepressant arm (single events of anxiety, depression, depressive
Esketamine was statistically signifcant at day 28 and demonstrated clinical improvement at earlier time points
AE = Adverse events
CAPS-5 = The Clinician-Administered PTSD Scale for DSM-5
CI = Confdence interval
df = Degrees of freedom
DSM-5 = The Diagnostic and Statistical Manual of Mental Disorders
MADRS = Montgomery-Åsberg Depression Rating Scale
MMRM = Mixed-Efect Model Repeated Measure (MMRM) mode
SD = Standard deviation
The following is a list of psychedelics and other psychoactive substances and corresponding clinical trial indications currently in multiple phases of study. This is not an all-inclusive list.67
LSD MDD, anxiety
MDMA PTSD, anxiety, social anxiety in autistic adults, chronic noncancer pain
PSYLOCYBIN TRD, MDD, MDD in cancer patients, alcohol use disorder, anxiety, smoking cessation
CANNABIS Acute and chronic pain, cancer-related symptoms, ADHD
KETAMINE MDD, PTSD, TRD, acute and chronic pain, suicidal ideation, depression in cancer patients, autism
REGULATORY TRENDS
Although the increased interest and research into psychedelic-assisted therapies grows, research, advocacy, and education organizations understand that arriving in the clinical setting needs to happen with regulations and oversight to ensure safety and appropriate uptake. The FDA is working closely with MAPS and other organizations in an efort to manage the development and application of potential life-saving psychedelic treatments.
MAPS was granted FDA’s “Breakthrough Therapy” designation in 2017 for MDMA-assisted psychotherapy for PTSD.68 A fnal FDA decision could come in 2023. In 2018 the FDA granted Compass Pathways “Breakthrough Therapy” designation for psilocybin-assisted therapy for the treatment of TRD and they are currently conducting a phase 2 trial in 216 participants with TRD in 22 sites in the US and Europe.69 Usona Institute was also granted “Breakthrough Therapy” designation in 2019 for psilocybin-assisted therapy in the treatment of MDD and has launched a phase 2 trial including 80 participants across 7 sites in the US.70 FDA’s “Breakthrough Therapy” designation as defned by the agency, “is for a drug that treats a serious or life-threatening condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement on a clinically signifcant endpoint(s) over available therapies.”71 This designation will allow sponsors to closely work with the FDA as the products are in development.
In December 2019, the FDA agreed to a MAPS Expanded Access program for MDMA-assisted psychotherapy for PTSD.72 This allows treatment-resistant patients with life-threatening conditions early access to treatment outside of the phase 3 clinical trial and will be a multisite, open-label, intermediate-size expanded access study under a treatment Investigational New Drug (IND). Earlier in 2019, Israel became the frst government to approve a Compassionate Use program for MDMA-assisted psychotherapy for MDMA.73 Oregon, the frst state to legalize psilocybin for clinical use in 2020, tasked the Oregon Health Authority (under Oregon Psilocybin Advisory Board guidance) with developing and implementing clinical psilocybin regulations by the end of 2022.74 75 Oregon might serve as a model as state-by-state legalization expands. Ann Arbor, Michigan, decriminalized psychedelic plants and fungi (ayahuasca, ibogaine, mescaline, peyote, psilocybin mushrooms and other substances with hallucinogenic properties) in September of 2020. Seattle, Washington became the largest US city to decriminalize cultivation and sharing of psychedelics (psilocybin mushrooms, ayahuasca, ibogaine and non-peyote-derived mescaline) in October of 2021.76, 77 In the coming wave of possible legalization and FDA approval, FDA oversight is likely to defne appropriate use in the areas of drug control, administration and setting along with federal, state and local laws governing their use.
DRUG SCHEDULING
The US Drug Enforcement Agency (DEA) categorizes drugs into 5 distinct schedules (Schedule I to V) depending on the drug’s acceptable medical use and the drug’s abuse or dependency potential.78 Schedule I drugs have no currently accepted medical use, a high potential for abuse, and the potential to create severe psychological and/or physical dependence. As the drug schedule changes, so does the abuse potential, with Schedule V drugs having the least abuse potential.
DRUG SCHEDULING 79
MDMA Schedule I
PSYLOCYBIN Schedule I
LSD Schedule I
MESCALINE Schedule I
DMT Schedule I
CANNABIS* Schedule I
KETAMINE Schedule III
ESKETAMINE Schedule III
DRUG LEGISLATION
*Cannabis is still a DEA Schedule I drug and currently is not FDA approved for the treatment of any condition or disease. A cannabis-derived drug product, Epidiolex (cannabidiol), is an FDA-approved prescription.80 A number of states allow medical marijuana, but it is illegal under federal law.81 In addition, users are not exempt from criminal prosecution depending on state law since it is prohibited at the federal level. State laws and regulations vary greatly.
As phase 3 trials continue for psychedelics, legalization for psychedelic-assisted psychotherapy will continue to be a focus for mental health conditions. Specifcally, the possible legalization of MDMA and psilocybin which have both shown promising results in early clinical trial reports. California is considering a bill that would decriminalize the use of psilocybin, MDMA, and multiple other psychedelics in group counseling settings.82
A recent development is the draft Cannabis Administration and Opportunity Act (CAOA).83 If legislation is fnalized, it would remove cannabis from the schedule as a controlled substance and legalize it at the federal level, while allowing states to determine their own cannabis policies. The COAO signals a change in the public and political view of cannabis. Federal cannabis reform could be the impetus for increased cannabis medical research, improve the social and economic lives of disproportionately impacted populations sufering from unfair discrimination or legal ramifcations, and may indicate a positive outlook for therapeutic psychedelic legalization.
NOTABLE MILESTONES
1967
The 1967 Convention on Drugs classifes LSD and other hallucinogens, under Schedule I
1986
1996
US Supreme Court allows importation of ayahuasca as a religious sacrament
2006 2017
Roland Grifth’s landmark paper is published in Psychopharmacology
MAPS receives FDA “Breakthrough Therapy” designation for MDMA-assisted psychotherapy for PTSD
MAPS is founded by Rick Doblin California legalizes medical marijuana
QUALITY STANDARDS
Since cannabis is not legal at the federal level, there is a lack of quality standards. These public standards are essential for safety and to prevent harm to patients and consumers. The United States Pharmacopeia (USP) is providing parameters to support the quality of cannabis for medicinal use, while policymakers develop the regulatory framework for federal legalization.84, 85 And, regardless of whether a psychedelic is naturally or synthetically derived, quality and purity are key to patient safety, GMP guidelines, and scale.
MAGELLAN’S PERSPECTIVE
Magellan Health supports fair and balanced reviews for new therapies to the market. We have four primary tenets of practice, including education, evidence-based, safety, and access. Our overarching perspectives for psychedelics are summarized in these four pillars:
Education & awareness
provide forward-facing education, awareness, and thought leadership for all stakeholders (payers, providers, patients, pharmacies, policymakers) on a new frontier while addressing the stigma associated with mental health and psychedelics as treatment options
Evidence-based recommendations & coverage
prepare for therapeutic psychedelics before they become mainstream, need highquality evidence of treatment efectiveness, and ensure future recommendations and coverage determinations are grounded in the clinical evidence
Patient safety
advocate for patients by encouraging quality and safety standards and processes, good manufacturing practices, as well as reliable delivery methods for any product on the market for medical use of psychedelics and cannabis
Responsible & sustainable access
engage in dialogue with infuencers regarding supply entering the market being approached in a manner that is responsible from a regulatory and legislative perspective as well as sustainable from a quality and supply chain angle
2019
2018
Compass Pathways receives FDA “Breakthrough Therapy” designation for psilocybin-assisted therapy in the treatment of TRD
Usona Institute receives FDA “Breakthrough Therapy” designation for psilocybin-assisted therapy in the treatment of MDD
FDA approves esketamine (Spravato®) nasal spray for TRD
The Johns Hopkin’s Center for Psychedelic and Consciousness Research is founded
2020
Oregon legalizes psilocybin-assisted psychotherapy for adults in controlled settings
2021
NIDA funds psilocybin study for tobacco cessation
CAOA to decriminalize cannabis is introduced as draft legislation
SUMMARY
Psychedelics have a long history of use in ritual and religious ceremonies, as well as plant-based treatment for a variety of physical and mental conditions in ancient cultures. Since the 1990’s the world has seen a marked increase in the interest of psychedelics and their potential in treating mental health conditions using psychedelic-assisted psychotherapy.
As mental health condition statistics progressively rise, healthcare professionals continue to look for efective ways to treat patients, specifcally treatment-resistant illness. COVID-19 has signifcantly increased symptoms of anxiety and depressive disorders, further necessitating the need for more efective, safe and tolerable treatments.
Ongoing funding and sponsorship continue to grow as proft and non-proft organizations, including US and international research institutions, advocacy and educational groups, universities and private researchers collaborate in their commitment to investigate the safety and efcacy of psychedelics such as psilocybin and MDMA for their potential use in treating mental illness. The FDA has granted “Breakthrough Therapy” designation for the study of psilocybin and MDMA marking further progress towards possible therapeutic use. Moreover, the recent federal funding to NIDA for psychedelic research, represents an infection point.
Movements to decriminalize and legalize psychedelics, as already seen in states like Oregon and California, will likely only extend to other states and local governments if early studies continue to report promising data.
Looking ahead, in 2023 MDMA-assisted psychotherapy for PTSD could reach a milestone if MAPS receives FDA approval. Preliminary clinical trial fndings suggest psychedelic-assisted psychotherapy can be efcacious in treating mental health disorders such as PTSD, addiction, and MDD, but more robust studies, as well as comparative trials, are needed to evaluate their safety and efcacy and optimal dosing. For psychedelics to become mainstream, they would need to be validated in large-scale randomized controlled trials.
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