Tryp Therapeuatics (TRYPF) Coverage Report

Exhibit 6: Sources of hallucinogens, by classic and dissociative Sources: April 2019 publication by National Institute on Drug Abuse; National Institutes of Health; and U.S. Department of Health and Human Services. Empathogens and entactogens: As their names imply, this class of psychedelics are most known for their abilities to generate empathy, sympathy, trust, connectedness. o MDMA “Ecstasy”: Following Merck’s discovery in 1912 while looking for an antihemorrhagic drug, Chemist Shulgin rediscovered MDMA in 1976 and published its psychoactive effects in 1978 (Ecstasy: The Complete Guide; Park Street Press, 2001), which likely sparked psychotherapists use and the illicit manufacturing and distribution as a party drug, “Ecstasy” in the early 1980s. o MDMA’s a broadly active drug in the brain as it impacts monoamine release, inhibits serotonin and norepinephrine transporter reuptake, inhibits monoamine oxidase, is a partial agonist of serotonin receptors 5-HT2 A , 5-HT1 A , and 5-HT2 C while increasing blood concentrations of oxytocin (Soc Neurosci. 2009; 4(4): 359, Psychopharmacology (Berl). 2017 Oct; 234(19): 2883, J Psychopharmacol. 2017 May; 31(5): 589, Handb Exp Pharmacol. 2018; 252: 143, Mol Pharmacol. 2003 Jun; 63(6) :1223). o In studies on healthy volunteers in clinical settings MDMA generated a controllable and reversible state of altered consciousness characterized by euphoria, empathy, well-being, insightfulness, extraversion, positive mood, gregariousness, feelings of authenticity, increased access to emotionally intense material, increased interpersonal trust, and compassion for oneself and others (J Psychopharmacol. 2017 May; 31(5): 589, Neurosci Biobehav Rev. 2015; 57: 433, Neuropharmacology. 2018; 142: 179, J Psychoactive Drugs. Jan-Mar 2014; 46: 37, J Psychopharmaco. 2016; 30(4): 378, J Psychopharmacol. 2014; 28(11): 1001). While there are reports of troublesome adverse events, including anxiety, grief, fear, and rage in clinical settings (Lancet Psychiatry. 2018; 5(6): 486, J Psychopharmacol. 2011; 25(4): 439), MDMA- assisted psychotherapy recently demonstrated impressive efficacy in 90 PTSD patients, randomized 1:1 vs. placebo, including less frequent adverse events than placebo (Nat Med. 2021 Jun;27(6):1025-1033). Hallucinogenic Source Notes LSD (D-lysergic acid diethylamide) Made from lysergic acid, a fungus that grows on rye and other grains. One of the most powerful mind-altering chemicals. It is a clear or white odorless material. Psilocybin (4-phosphoryloxy- N,N- dimethyltryptamine) From certain types of mushrooms found in tropical and subtropical regions of South America, Mexico, and the U.S. Can also be synthetic. Peyote (mescaline) From a small, spineless cactus with mescaline as its main ingredient. Can also be synthetic. DMT/Ayahuasca (N,N- dimethyltryptamine) DMT is found in the leaves of the Amazon's Psychotria viridis shrub. Ayahuasca includes Banisteriopsis caapi , which is also hallucinogenic. Can also be synthetic. PCP (Phencyclidine) Synthesized in 1926 and marketed by Parke-Davis in the 1950s as an IV anesthetic. PCP is made relatively cheaply in clandestine labs. Used today by veternarians, high-grade PCP is diverted for illicit use. Ketamine (2-(2-Chlorophenyl)-2- (methylamino)cycloh exanone HCl) Synthesized in 1962 and marketed in the 1970s by Parke- Davis, it was used in the Vietnam War as an anesthetic due to its relative safety. Ketamine is made relatively cheaply in clandestine labs. Used today by veternarians, high-grade PCP is diverted for illicit use. DXM (dextromethorphan) Discovered in 1952 as a combination from two isomers. Approved for pseudobulbar affects, its OTC use as a cough suppressent has been limited globally due to its illicit use. Salvia (Salvia divinorum) From a plant commonly used by the Mazatecas of southern Mexico and Central and South America. Not known to be commonly synthesized and/or manufactured. Research not advanced to clinical stage by any companies (ClinicalTrials.gov) Classic Dissociative Michael Higgins 212.409.2074 Tryp Therapeutics, Inc. (TRYPF) Page 13