Tryp Therapeuatics (TRYPF) Coverage Report

for post-traumatic stress disorder (PTSD), MDMA failed to show any abuse potential (Nat Med. 2021; 27(6): 1025). Exhibit 14: Comparison of acute lethality of psychoactive substances Sources: Addiction. 2004 Jun;99(6):686-96 and Ladenburg Thalmann research Specifically for psilocybin, in drug discrimination studies with amphetamine, psilocybin does not generalize to amphetamine, and it does not substitute for amphetamine in amphetamine trained animals (Neuropharmacology. 2018 Nov; 142:143). In ICSS studies, psilocybin failed to show reliable ICSS facilitation (Exp Clin Psychopharmacol. 2019; 27(3): 215). The US Public Health Service Addiction Research Center (ARC) of the National Institute of Mental Health developed two scales to access abuse liability in humans. The Morphine Benzedrine Group (MBG) scale and the LSD scale. The MBG scale is a predictor of abuse liability, and the LSD scale is the dysphoria and psychotomimetic scale, which is a predictor of low abuse liability. Psilocybin consistently shows an increase on the LSD scale, but depending on the dosage and individual being tested, can also show elevated scores on the MBG. However, these elevated MBG scores are still lower than those seen with opioids and stimulants (Neuropharmacology. 2018 Nov; 142:143). Lack of abuse potential is also supported by a study in the UK, as 20 drugs that are considered harmful were evaluated by members of the Independent Scientific Committee on Drugs. They evaluated these drugs on 16 criteria, nine related to the harms that a drug produces in the user and seven to the harms to others. As shown in Exhibit 15, Generic name Safety ratio Lethal dose (range) Effective dose (range) References > 15 g 15 mg Kalant et al. (1999), (–) (12–22) Heyndrickx et al. (1969) 100 mg 100 mg Fysh et al. (1985), (–) (25–200) Klock et al. 1975) Psilocybin (or) 1 1,000 6g (–) Gerault & Picart (1996) > 525 L Garriot & Petty (1980) (–) Winek (1995) Prozac (or) 100 > 2 g 20 mg Goeringer et al . (2000), 2 g 40 mg Gillin et al. (1976), (–) (34–70) Callaway et al. (1999) 5 g 100 mg Druid & Holmgren (1997) (1.5–8) (60–120) Ekwall (1998) 2.7 g 70 mg Green et al. (1999), (–) (20–150) Moore et al. (1997) 8.4 g 350 mg Henry et al . (2003), (–) (200–450) Nolte & Zumwalt (1999) 100 mg 5 mg Seymour et al . (2003) (20–420) (3–10) Worm et al . (1993) 2 g 125 mg Kalant (2001), (150–1,250) (15–150) Garcia-Repetto et al . (2003) 1,200 mg 80 mg Mittleman & Wetli (1984) (20–2,000) (40–90) Smart & Anglin (1987) 330 g 33 g Jones & Holmgren (2003) (276–455) (22–40) Ekwall & Clemedson (1997) 1.5 g 150 mg Dalpe-Scott et al. (–) (100–300) (1995), Rammer et al. (1988) > 150 mg 15 mg Logan et al . (1998), (140–1,650) (10–25) Wallace & Squires (2000) 50 mg 8 mg Meissner et al. (2002), (12–180) (5–10) Goldberger et al. 1994) im = intramuscular, inh = inhaled, in = intranasal, ip = intraperitoneal, iv = intravenous, or = oral, sm = smoked; 1 Animal data; 2 N 2 O when used with adequate oxygen is not lethal 15 10 10 10 6 >1,000 Dextromethorphan (or) Methamphetamine (or) Heroin (iv) 1,000 50 50 38 24 20 16 Marijuana (sm) LSD (or) 1 N,N-dimethyl-tryptamine (or) 1 Phenobarbital (or) Ketamine (in) 1 Mescaline (or) 1 Methadone (or) MDMA (or) Cocaine (in) Nitrous oxide (inh) 2 3.5 L (1.75–7) >150 Alcohol (or) Michael Higgins 212.409.2074 Tryp Therapeutics, Inc. (TRYPF) Page 21