Open-Label Dose-Ranging Study of Oral SM-001 in Healthy Adults

NCT05894902 | Unknown Phase 1 DMC FDA Drug

• 1 other identifier: SM-001
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

Phase I safety and dose finding study of a standardized Ayahuasca analog (SM-001) in healthy adult volunteers

Conditions

Major Depression; Post Traumatic Stress Disorder

Keywords

Banisteriopsis caapi; Psychotria viridis; ayahuasca; ethnomedicine; N,N-dimethyltryptamine (DMT); harmine (HAR); harmaline; tetrahydroharmine

Outcome Measures

Primary Outcomes (1)

• Primary Objective

  To evaluate safety and tolerability of SM-001 in healthy adults following a single oral dose, at one of three different dose levels. The Incidence of Treatment-Emergent Adverse Events will be assessed using the Common Terminology Criteria for Adverse Events (CTCAE). Percentage of participants with at least one safety event \[Time Frame: Baseline up to Day 28 \] Safety will be evaluated by the monitoring of adverse events (AEs), vital signs, blood pressure, heart rate, pulse oximetry, electrocardiogram (ECG) evaluations, clinical laboratory assessments and physical examination findings.

  1-28 days

Secondary Outcomes (5)

• Short-term psychological impact

  24 hours after single drug session

• Longer-term psychological impact

  Day 7 after a single drug session

• Bioavailability of SM-001

  Day 1-2

• Effects of a single dose of SM-001 on blood levels of brain derived nerve growth factor

  Day 1-28

• Effects of a single dose of SM-001 on blood cortisol blood levels

  Day 1 - 28

Study Arms (3)

Open label Phase I safety & dose finding study: low dose group

ACTIVE COMPARATOR

4 study participants will receive a low oral dose (0.5 mL/Kg) of SM-001

Drug: SM-001

Open label Phase I safety & dose finding study: medium dose group

ACTIVE COMPARATOR

4 study participants will receive a medium oral dose (1.0 mL/Kg) of SM-001

Drug: SM-001

Open label Phase I safety & dose finding study: high dose group

ACTIVE COMPARATOR

4 study participants will receive a high oral dose (2.0 mL/Kg) of SM-001

Drug: SM-001

Interventions

SM-001 DRUG

The Investigational New Drug SM-001 is formulated as a hot water decoction of two proprietary clonal cultivars of the Peruvian plants, Banisteriopsis caapi (BC) and Psychotria viridis (PV).

Also known as: Ayahuasca

Open label Phase I safety & dose finding study: high dose group; Open label Phase I safety & dose finding study: low dose group; Open label Phase I safety & dose finding study: medium dose group

Eligibility Criteria

• Age: 25 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy adults: men and women ages 25-65 years of age
• Previous experience with a psychedelic drug
• Vital Signs within normal limits for temperature (oral), respiratory rate, heart rate
• Normal blood pressure (for age) in the absence of antihypertensive drugs
• Normal complete blood count and differential, platelets, coagulation ((PT/PTT)
• Liver function tests ≤ 1.5X upper limits of normal
• Renal function (BUN, serum Creatinine) - within normal limits
• Able to understand and willing to comply with Study Protocol requirements.
• Willing to abstain from alcohol for at least 72 hours prior to and following Study Day 0
• No use of recreational drugs for at least 14 days prior to Study Day 0.
• Women who are not pregnant or lactating.

You may not qualify if:

• Body Mass Index \> 30 or \< 20
• Systemic condition that includes, but is not limited to: hematological, immunological, hepatic, renal, cardiac, neurological conditions that is under current treatment or causes abnormal physical or laboratory parameters.
• History of seizures
• History of drug or alcohol abuse
• History of psychiatric disorder or history of significant trauma, as defined by DSM- V.
• Use of SSRIs, MAO inhibitors, or other psychoactive compounds either pharmaceutical drugs or botanical in origin (i.e., 5-HTP, St John's Wort)
• Any condition which, in the opinion of the Investigators, would preclude the use of the test article or the successful completion of the study.

Sponsors & Collaborators

• Advanced Integrative Medical Science Institute: lead

Study Sites (1)

AIMS Institute

Seattle, Washington, 98102, United States

Location

Related Publications (36)

• Aarons DH, Rossi GV, Orzechowski RF. Cardiovascular actions of three harmala alkaloids: harmine, harmaline, and harmalol. J Pharm Sci. 1977 Sep;66(9):1244-8. doi: 10.1002/jps.2600660910.

  PMID: 903860 BACKGROUND

• Barrett FS, Johnson MW, Griffiths RR. Validation of the revised Mystical Experience Questionnaire in experimental sessions with psilocybin. J Psychopharmacol. 2015 Nov;29(11):1182-90. doi: 10.1177/0269881115609019. Epub 2015 Oct 6.

  PMID: 26442957 BACKGROUND

• Brown CS, Bryant SG. Monoamine oxidase inhibitors: safety and efficacy issues. Drug Intell Clin Pharm. 1988 Mar;22(3):232-5. doi: 10.1177/106002808802200311.

  PMID: 3284731 BACKGROUND

• Hamill J, Hallak J, Dursun SM, Baker G. Ayahuasca: Psychological and Physiologic Effects, Pharmacology and Potential Uses in Addiction and Mental Illness. Curr Neuropharmacol. 2019;17(2):108-128. doi: 10.2174/1570159X16666180125095902.

  PMID: 29366418 BACKGROUND

• Callaway JC, Raymon LP, Hearn WL, McKenna DJ, Grob CS, Brito GS, Mash DC. Quantitation of N,N-dimethyltryptamine and harmala alkaloids in human plasma after oral dosing with ayahuasca. J Anal Toxicol. 1996 Oct;20(6):492-7. doi: 10.1093/jat/20.6.492.

  PMID: 8889686 BACKGROUND

• Da Prada M, Zurcher G, Wuthrich I, Haefely WE. On tyramine, food, beverages and the reversible MAO inhibitor moclobemide. J Neural Transm Suppl. 1988;26:31-56.

  PMID: 3283290 BACKGROUND

• dos Santos RG. Safety and side effects of ayahuasca in humans--an overview focusing on developmental toxicology. J Psychoactive Drugs. 2013 Jan-Mar;45(1):68-78. doi: 10.1080/02791072.2013.763564.

  PMID: 23662333 BACKGROUND

• Dos Santos RG, Grasa E, Valle M, Ballester MR, Bouso JC, Nomdedeu JF, Homs R, Barbanoj MJ, Riba J. Pharmacology of ayahuasca administered in two repeated doses. Psychopharmacology (Berl). 2012 Feb;219(4):1039-53. doi: 10.1007/s00213-011-2434-x. Epub 2011 Aug 13.

  PMID: 21842159 BACKGROUND

• Santos RG, Landeira-Fernandez J, Strassman RJ, Motta V, Cruz AP. Effects of ayahuasca on psychometric measures of anxiety, panic-like and hopelessness in Santo Daime members. J Ethnopharmacol. 2007 Jul 25;112(3):507-13. doi: 10.1016/j.jep.2007.04.012. Epub 2007 Apr 25.

  PMID: 17532158 BACKGROUND

• Dominguez-Clave E, Soler J, Elices M, Pascual JC, Alvarez E, de la Fuente Revenga M, Friedlander P, Feilding A, Riba J. Ayahuasca: Pharmacology, neuroscience and therapeutic potential. Brain Res Bull. 2016 Sep;126(Pt 1):89-101. doi: 10.1016/j.brainresbull.2016.03.002. Epub 2016 Mar 11.

  PMID: 26976063 BACKGROUND

• Gable RS. Risk assessment of ritual use of oral dimethyltryptamine (DMT) and harmala alkaloids. Addiction. 2007 Jan;102(1):24-34. doi: 10.1111/j.1360-0443.2006.01652.x.

  PMID: 17207120 BACKGROUND

• Gillin JC, Tinklenberg J, Stoff DM, Stillman R, Shortlidge JS, Wyatt RJ. 5-Methoxy-N,N-dimethyltryptamine: behavioral and toxicological effects in animals. Biol Psychiatry. 1976 Jun;11(3):355-8. No abstract available.

  PMID: 820383 BACKGROUND

• Griffiths R, Richards W, Johnson M, McCann U, Jesse R. Mystical-type experiences occasioned by psilocybin mediate the attribution of personal meaning and spiritual significance 14 months later. J Psychopharmacol. 2008 Aug;22(6):621-32. doi: 10.1177/0269881108094300. Epub 2008 Jul 1.

  PMID: 18593735 BACKGROUND

• Grob CS, McKenna DJ, Callaway JC, Brito GS, Neves ES, Oberlaender G, Saide OL, Labigalini E, Tacla C, Miranda CT, Strassman RJ, Boone KB. Human psychopharmacology of hoasca, a plant hallucinogen used in ritual context in Brazil. J Nerv Ment Dis. 1996 Feb;184(2):86-94. doi: 10.1097/00005053-199602000-00004.

  PMID: 8596116 BACKGROUND

• Kamel SH, Ibrahim TM, Hamza SM. Effect of harmine and harmaline hydrochloride on pregnancy in white rats. Zentralbl Veterinarmed A. 1971 May;18(3):230-3. doi: 10.1111/j.1439-0442.1971.tb00573.x. No abstract available.

  PMID: 4997511 BACKGROUND

• Luna LE. The healing practices of a Peruvian shaman. J Ethnopharmacol. 1984 Jul;11(2):123-33. doi: 10.1016/0378-8741(84)90035-7.

  PMID: 6387284 BACKGROUND

• Marwood JF, Huston V, Wall KT. Some cardiovascular effects of monoamine oxidase inhibitors in unanaesthetized rats. Clin Exp Pharmacol Physiol. 1985 Mar-Apr;12(2):161-8. doi: 10.1111/j.1440-1681.1985.tb02319.x.

  PMID: 3839173 BACKGROUND

• McCabe BJ. Dietary tyramine and other pressor amines in MAOI regimens: a review. J Am Diet Assoc. 1986 Aug;86(8):1059-64.

  PMID: 3525654 BACKGROUND

• McKenna DJ. Ayahuasca and human destiny. J Psychoactive Drugs. 2005 Jun;37(2):231-4. doi: 10.1080/02791072.2005.10399805.

  PMID: 16149337 BACKGROUND

• McKenna DJ, Towers GH, Abbott F. Monoamine oxidase inhibitors in South American hallucinogenic plants: tryptamine and beta-carboline constituents of ayahuasca. J Ethnopharmacol. 1984 Apr;10(2):195-223. doi: 10.1016/0378-8741(84)90003-5.

  PMID: 6587171 BACKGROUND

• Naranjo P. Hallucinogenic plant use and related indigenous belief systems in the Ecuadorian Amazon. J Ethnopharmacol. 1979 Apr;1(2):121-45. doi: 10.1016/0378-8741(79)90003-5.

  PMID: 542010 BACKGROUND

• O'Hearn E, Molliver ME. Degeneration of Purkinje cells in parasagittal zones of the cerebellar vermis after treatment with ibogaine or harmaline. Neuroscience. 1993 Jul;55(2):303-10. doi: 10.1016/0306-4522(93)90500-f.

  PMID: 8377927 BACKGROUND

• Oliveira CD, Moreira CQ, de Sa LR, Spinosa Hde S, Yonamine M. Maternal and developmental toxicity of ayahuasca in Wistar rats. Birth Defects Res B Dev Reprod Toxicol. 2010 Jun;89(3):207-12. doi: 10.1002/bdrb.20244.

  PMID: 20549682 BACKGROUND

• Palhano-Fontes F, Andrade KC, Tofoli LF, Santos AC, Crippa JA, Hallak JE, Ribeiro S, de Araujo DB. The psychedelic state induced by ayahuasca modulates the activity and connectivity of the default mode network. PLoS One. 2015 Feb 18;10(2):e0118143. doi: 10.1371/journal.pone.0118143. eCollection 2015.

  PMID: 25693169 BACKGROUND

• Pic-Taylor A, da Motta LG, de Morais JA, Junior WM, Santos Ade F, Campos LA, Mortari MR, von Zuben MV, Caldas ED. Behavioural and neurotoxic effects of ayahuasca infusion (Banisteriopsis caapi and Psychotria viridis) in female Wistar rat. Behav Processes. 2015 Sep;118:102-10. doi: 10.1016/j.beproc.2015.05.004. Epub 2015 Jun 3.

  PMID: 26049017 BACKGROUND

• Pitol DL, Siessere S, Dos Santos RG, Rosa ML, Hallak JE, Scalize PH, Pereira BF, Iyomasa MM, Semprini M, Riba J, Regalo SC. Ayahuasca Alters Structural Parameters of the Rat Aorta. J Cardiovasc Pharmacol. 2015 Jul;66(1):58-62. doi: 10.1097/FJC.0000000000000243.

  PMID: 25714595 BACKGROUND

• Riba J, McIlhenny EH, Valle M, Bouso JC, Barker SA. Metabolism and disposition of N,N-dimethyltryptamine and harmala alkaloids after oral administration of ayahuasca. Drug Test Anal. 2012 Jul-Aug;4(7-8):610-6. doi: 10.1002/dta.1344. Epub 2012 Apr 19.

  PMID: 22514127 BACKGROUND

• Riba J, Rodriguez-Fornells A, Strassman RJ, Barbanoj MJ. Psychometric assessment of the Hallucinogen Rating Scale. Drug Alcohol Depend. 2001 May 1;62(3):215-23. doi: 10.1016/s0376-8716(00)00175-7.

  PMID: 11295326 BACKGROUND

• Kiraga MK, Mason NL, Uthaug MV, van Oorsouw KIM, Toennes SW, Ramaekers JG, Kuypers KPC. Persisting Effects of Ayahuasca on Empathy, Creative Thinking, Decentering, Personality, and Well-Being. Front Pharmacol. 2021 Oct 1;12:721537. doi: 10.3389/fphar.2021.721537. eCollection 2021.

  PMID: 34658861 BACKGROUND

• Cameron LP, Benson CJ, Dunlap LE, Olson DE. Effects of N, N-Dimethyltryptamine on Rat Behaviors Relevant to Anxiety and Depression. ACS Chem Neurosci. 2018 Jul 18;9(7):1582-1590. doi: 10.1021/acschemneuro.8b00134. Epub 2018 Apr 24.

  PMID: 29664276 BACKGROUND

• Sklerov J, Levine B, Moore KA, King T, Fowler D. A fatal intoxication following the ingestion of 5-methoxy-N,N-dimethyltryptamine in an ayahuasca preparation. J Anal Toxicol. 2005 Nov-Dec;29(8):838-41. doi: 10.1093/jat/29.8.838.

  PMID: 16356341 BACKGROUND

• Strassman RJ, Qualls CR, Uhlenhuth EH, Kellner R. Dose-response study of N,N-dimethyltryptamine in humans. II. Subjective effects and preliminary results of a new rating scale. Arch Gen Psychiatry. 1994 Feb;51(2):98-108. doi: 10.1001/archpsyc.1994.03950020022002.

  PMID: 8297217 BACKGROUND

• Bilhimer MH, Schult RF, Higgs KV, Wiegand TJ, Gorodetsky RM, Acquisto NM. Acute Intoxication following Dimethyltryptamine Ingestion. Case Rep Emerg Med. 2018 Feb 27;2018:3452691. doi: 10.1155/2018/3452691. eCollection 2018.

  PMID: 29682363 BACKGROUND

• Wehner FC, Thiel PG, van Rensburg SJ. Mutagenicity of alkaloids in the Salmonella/microsome system. Mutat Res. 1979 Feb;66(2):187-90. doi: 10.1016/0165-1218(79)90065-x. No abstract available.

  PMID: 372800 BACKGROUND

• Wiltshire PE, Hawksworth DL, Edwards KJ. Light microscopy can reveal the consumption of a mixture of psychotropic plant and fungal material in suspicious death. J Forensic Leg Med. 2015 Aug;34:73-80. doi: 10.1016/j.jflm.2015.05.010. Epub 2015 Jun 4.

  PMID: 26165663 BACKGROUND

• Yritia M, Riba J, Ortuno J, Ramirez A, Castillo A, Alfaro Y, de la Torre R, Barbanoj MJ. Determination of N,N-dimethyltryptamine and beta-carboline alkaloids in human plasma following oral administration of Ayahuasca. J Chromatogr B Analyt Technol Biomed Life Sci. 2002 Nov 5;779(2):271-81. doi: 10.1016/s1570-0232(02)00397-5.

  PMID: 12361741 BACKGROUND

MeSH Terms

Conditions

Depressive Disorder, Major; Stress Disorders, Post-Traumatic

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Stress Disorders, Traumatic; Trauma and Stressor Related Disorders

Study Officials

• Leanna J Standish, ND PhD

  AIMS Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Leanna J Standish, ND PhD

CONTACT

2064201321; Lstandish@aimsinstitute.net

Sunil K Aggarwal, MD PhD

CONTACT

2064201321; saggarwal@aimsinstitute.net

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Subjects will be consecutively accrued to one of three study groups, starting at the lowest dose, Level 1 ("low" dose), and proceeding to the next higher dose level. Each subject will receive one dose of the Study Drug orally at the Clinical Study Site, according to their assigned dose Level. Dose levels vary by volume: Level 1: 0.5 mL/kg ("low"; 50% of usual dose) N=4 (2M/2F) Level 2: 1 ml/kg ("medium"; 100% of usual dose) N=4 (2M/2F) Level 3: 2 ml/kg ("high"; 200% of usual dose) N=4 (2M/2F)

Study Record Dates

• First Submitted: March 15, 2023
• First Posted: June 8, 2023
• Study Start: October 1, 2023
• Primary Completion: April 30, 2024
• Study Completion: June 30, 2024
• Last Updated: July 7, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)