PMID- 35987353
OWN - NLM
STAT- MEDLINE
DCOM- 20220913
LR  - 20220915
IS  - 1873-7064 (Electronic)
IS  - 0028-3908 (Linking)
VI  - 218
DP  - 2022 Nov 1
TI  - Psychedelic drug abuse potential assessment research for new drug applications 
      and Controlled Substances Act scheduling.
PG  - 109220
LID - S0028-3908(22)00279-9 [pii]
LID - 10.1016/j.neuropharm.2022.109220 [doi]
AB  - New medicines containing classic hallucinogenic and entactogenic psychedelic 
      substance are under development for various psychiatric and neurological 
      disorders. Many of these, including psilocybin, lysergic acid diethylamide (LSD), 
      and 3,4-methylenedioxymethamphetamine (MDMA) are Schedule I controlled substances 
      of the United States Controlled Substances Act (US CSA), and similarly controlled 
      globally. The implications of the CSA for research and medicines development, the 
      path to approval of medicines, and their subsequent removal from Schedule I in 
      the US are discussed. This entire process occurs within the framework of the CSA 
      in the US and its counterparts internationally in accordance with international 
      drug control treaties. Abuse potential related research in the US informs the 
      eight factors of the CSA which provide the basis for rescheduling actions that 
      must occur upon approval of a drug that contains a Schedule I substance. 
      Abuse-related research also informs drug product labeling and the risk evaluation 
      and mitigation strategies (REMS) will likely be required for approved medicines. 
      Human abuse potential studies typically employed in CNS drug development may be 
      problematic for substances with strong hallucinogenic effects such as psilocybin, 
      and alternative strategies are discussed. Implications for research, medicinal 
      development, and controlled substance scheduling are presented in the context of 
      the US CSA and FDA requirements with implications for global regulation. We also 
      discuss how abuse-related research can contribute to understanding mechanisms of 
      action and therapeutic effects as well as the totality of the effects of the 
      drugs on the brain, behavior, mood, and the constructs of spirituality and 
      consciousness.
CI  - Copyright (c) 2022. Published by Elsevier Ltd.
FAU - Henningfield, Jack E
AU  - Henningfield JE
AD  - PinneyAssociates, Inc, 4800 Montgomery Lane, Suite 400, Bethesda, MD, USA; 
      Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School 
      of Medicine, Baltimore, MD, USA. Electronic address: 
      jhenning@pinneyassociates.com.
FAU - Coe, Marion A
AU  - Coe MA
AD  - PinneyAssociates, Inc, 4800 Montgomery Lane, Suite 400, Bethesda, MD, USA.
FAU - Griffiths, Roland R
AU  - Griffiths RR
AD  - Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School 
      of Medicine, Baltimore, MD, USA.
FAU - Belouin, Sean J
AU  - Belouin SJ
AD  - Substance Abuse and Mental Health Services Administration, Rockville, MD, USA.
FAU - Berger, Ann
AU  - Berger A
AD  - Chief of Pain and Palliative Care, Senior Research Clinician (Full Professor). 
      National Institutes of Health Clinical Center, Bethesda, MD, USA.
FAU - Coker, Allison R
AU  - Coker AR
AD  - MAPS Public Benefit Corporation (MAPS PBC), San Jose, CA, USA; Department of 
      Neurology, University of California, San Francisco, CA, USA.
FAU - Comer, Sandra D
AU  - Comer SD
AD  - Columbia University, Irving Medical Center, New York State Psychiatric Institute, 
      New York, NY, USA.
FAU - Heal, David J
AU  - Heal DJ
AD  - DevelRx Ltd. BioCity, Nottingham, And Department of Pharmacy and Pharmacology 
      University of Bath, Bath, UK.
FAU - Hendricks, Peter S
AU  - Hendricks PS
AD  - Department of Health Behavior, School of Public Health, University of Alabama at 
      Birmingham, USA.
FAU - Nichols, Charles D
AU  - Nichols CD
AD  - Department of Pharmacology and Experimental Therapeutics, Louisiana State 
      University Health Sciences Center, USA.
FAU - Sapienza, Frank
AU  - Sapienza F
AD  - Partner, The Drug and Chemical Advisory Group, LLC, Fairfax, VA, USA.
FAU - Vocci, Frank J
AU  - Vocci FJ
AD  - Friends Research Institute, Baltimore, MD, USA.
FAU - Zia, Farah Z
AU  - Zia FZ
AD  - Department of Health & Human Services National Institutes of Health, National 
      Cancer Institute Division of Cancer Treatment & Diagnosis, Washington, DC, USA.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20220817
PL  - England
TA  - Neuropharmacology
JT  - Neuropharmacology
JID - 0236217
RN  - 0 (Controlled Substances)
RN  - 0 (Hallucinogens)
RN  - 2RV7212BP0 (Psilocybin)
RN  - 8NA5SWF92O (Lysergic Acid Diethylamide)
SB  - IM
MH  - Controlled Substances
MH  - *Hallucinogens/pharmacology/therapeutic use
MH  - Humans
MH  - Lysergic Acid Diethylamide/pharmacology/therapeutic use
MH  - Psilocybin/therapeutic use
MH  - *Substance-Related Disorders/drug therapy
MH  - United States
OTO - NOTNLM
OT  - Abuse liability
OT  - Clinical study design
OT  - Consciousness
OT  - Controlled substance regulation
OT  - Drug scheduling
OT  - Psychedelics
EDAT- 2022/08/21 06:00
MHDA- 2022/09/14 06:00
CRDT- 2022/08/20 19:33
PHST- 2022/04/26 00:00 [received]
PHST- 2022/07/05 00:00 [revised]
PHST- 2022/08/09 00:00 [accepted]
PHST- 2022/08/21 06:00 [pubmed]
PHST- 2022/09/14 06:00 [medline]
PHST- 2022/08/20 19:33 [entrez]
AID - S0028-3908(22)00279-9 [pii]
AID - 10.1016/j.neuropharm.2022.109220 [doi]
PST - ppublish
SO  - Neuropharmacology. 2022 Nov 1;218:109220. doi: 10.1016/j.neuropharm.2022.109220. 
      Epub 2022 Aug 17.