what is a “designer drug”? · 2018-03-26 · designer drug is an informal term for ... botteon...
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"Technological Approaches in the Synthesis of
Designer Drugs, and Creative Prosecution of the
Non-Scheduled, Illicit, Analogue Drug"
David M. Benjamin, Ph.D.
Clinical Pharmacologist & Toxicologist
Adjunct Associate Professor, Dept. of Pharmaceutical Sciences,
Northeastern University, Boston, MA
Fellow, American Academy of Forensic Sciences (Toxicology)
Fellow, American Society for Healthcare Risk Management
Fellow, American College of Clinical Pharmacology
Fellow, American College of Legal Medicine
Member, Society of Forensic Toxicologists
What is a “Designer Drug”?
Designer drug is an informal term for
psychoactive drugs that are related, by
structure and/or activity, to existing
psychoactive drugs frequently used for
“recreational” use.
In many instances, designer drugs have been
synthesized by small chemical modifications
of known active drugs, and
Resemble the “parent” drug as: structural
analogues, stereoisomers and derivatives of
those drugs.
Federal Analog Act
Controlled Substance Analogue Enforcement Act of
1986
Effective October 27, 1986
Federal Analog Act, 21 U.S.C. § 813, is a section of
the United States Controlled Substances Act which
allowed any chemical "substantially similar" to a
controlled substance listed in Schedule I or II to be
treated as if it were also listed in those schedules, but
only if intended for human consumption. These
similar substances are often called designer drugs.*
*Wikipedia, accessed January 11,2014.
Substantially Similar
Substantially similar means that the chemical
structures are very similar
Substantially similar does not mean exactly the same;
some level of difference is acceptable and all experts
do not agree
Substantially similar can be: (1) a readily cognizable
(chemical) similarity between the alleged analog
and the controlled substance prior to ingestion, (2)
has a CNS effect equal to or greater than the
substance scheduled in C-I or C-II, or (3) is
metabolized to the alleged the controlled substance
analog after ingestion, e.g., 1, 4 – butanediol -> GHB
Classification of
Designer Drugs by Chemistry Legislation
Control by classes
Analogs (Chemical groups)
Compounds:
e.g., Spice, K-2
Designer stimulants, e.g.
Cathinones, bath salts
Synthetic cannabinoids,
Benzylpiperazines
Phenethylamines
Tryptamines
Pyrrolidinophenones
My thanks to Heather L. Harris, MFS, JD, D-ABC for permission to use
her slides.
Synthetic Drug Abuse Prevention
Act of 2012 – Chemical Classes Naphthoxylindoles
Naphthylmethylindoles
Naphthoylpyrroles
Naphthylmethylindenes
Phenylacetylindoles
Cyclohexylphenols
Benzoylindoles
Adamantoylindoles
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Chemical Structure of THC vs. Synthetic
Cannabinoids – Substantially Similar?
THC; Tetrahydrocannabinol (−)-trans-Δ9- tetrahydrocannabinol,
a dibenopyran.
CP-47,497 has been identified
in Spice.
Modified from: Synthetic Cannabinoids
The Challenges of Testing for Designer Drugs
By Bridgit O. Crews, PhD
February 2013 Clinical Laboratory
News: Volume 39, Number 2 Accessed online: Jan. 4,2014
Mechanism of Action of the
Cannabinoids
Neurotransmitter (NT) from
presynaptic neuron activates the
postsynaptic neuron.
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3
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Endogenous and Exogenous
Cannabinoids Reduce Neuronal Signaling
Postsynaptic
Neuron
Neurotransmitter
Receptor
Endogenous
Cannabinoid
Retrograde Signaling
CB1 Receptor
Presynaptic
Neuron
Inhibition of
Neurotransmitter
Release
Cannabinoid Therapy
Activated postsynaptic neuron
releases endocannabinoids.
Endogenous CB1 ligand diffuses
back to and binds to the
presynaptic CB1 receptor.
CB1 receptor activates a G-
protein, leading to inhibition of
NT release.
Synthetic Cannabinoids are
thought to activate CB1
receptors directly, mimicking the
effects of endocannabinoids.
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CB1
CB2
High-affinity nerve growth factor
CGRP=calcitonin gene-related peptide
5-HT=5-hydroxytryptamine
NGF=nerve growth factor
NO=nitric oxide
Adapted from Lynch M. Pain Res Manage. 2005;10(suppl A):7A-14A. Gwen DeCelles, MFA, Medical Illustrator.
CB1 Effects
CGRP
NGF
Plasma extravasation
Hyperalgesia
Edema
CB2 Effects
Mast cell degranulation
Histamine
5-HT
NGF sensitization
Neutrophil migration
NO production by
macrophages
Effects of Cannabinoid Receptors
in Pain Neuromodulation
Cathinones in “Bath Salts”
Mephedrone (Miaow
Miaow)
(4-methylmethcathinone, 4-
MMC)
Methylone
(βk-MDMA, 3,4-
methylenedioxy-N-
methylcathinone)
MDPV (3,4-
methylenedioxypyrovalerone)
Cathinones
Mephedrone (Miaow
Miaow)
(4-methylmethcathinone, 4-
MMC)
Methylone
(βk-MDMA, 3,4-
methylenedioxy-N-
methylcathinone)
MDPV (3,4-
methylenedioxypyrovalerone)
Cathinone ADRs Kesha,K., Boggs, CL, Allan, CH, et al., MDPV (“Bath Salts”) Related Death:
Case Report and Review of the Lit., JFS 2013;58:(6)1654-1680.
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Grazie, Drs. Papanti, Schifano &
Botteon for this great paper!
From: “Spiceophrenia”: a systematic
overview of “Spice”-related
psychopathological issues and a case report.
Duccio Papanti, Fabrizio Schifano, Giulia
Botteon, et al. Hum. Psychopharmacol Clin
Exp 2013; 28: 379–389.
Spice drugs and
psychopathological ADRs -1
Situational anxiety, agitation
*Recurrent psychotic episodes triggered
by cannabis
“Spice” Anxiety, psychotic symptoms;
hallucinations
16 year old “Spice” Altered mental status
Visual hallucinations, agitation, restlessness
and anxiety
*Long-lasting psychotic episodes
Spice drugs and
psychopathological ADRs -2
“Spice” Severe anxiety and paranoia,
auditory and visual hallucinations, halted
speech
Anxiety, anger, euphoria/sadness, irritability,
restlessness, memory changes, auditory/visual
perceptual changes, paranoid thoughts.
Subjects had no psychiatric history before
using Synthetic Cannabinoids.
Spice drugs and
psychopathological ADRs -3
*Long-lasting psychotic episodes and
substance-induced psychosis (auditory and
visual hallucinations, paranoid delusions,
flat affect, thought blocking, disorganized
speech, alogia, psychomotor retardation,
agitation, suicidal ideation, anxiety,
dysthymia)
Spice drugs and
psychopathological ADRs - 4 Nonsensical speech, paranoia, delusions,
disorganization
Tremulousness, anxiety, confusion
Anxiety, disorientation, tremulousness,
“feeling psychotic”
Motor retardation, auditory and visual
hallucinations
Delusions, aggressiveness, inappropriate
affect
Spice drugs and
psychopathological ADRs - 5
Sedation, confusion, disorientation, agitation
Unresponsiveness, agitation, paranoia,
delusions
Hx PTSD, brief substance-induced psychotic
episode; *2 of 3 positive for THC
“Spice”- Persistent psychosis after SC intake,
disorganized speech, poverty of thought,
Loosening of associations, paranoia,
suicidality
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Spice drugs and
psychopathological ADRs - 6
“Capgras delusions” a disorder in which a
person holds a delusion that a friend, spouse,
parent, or other close family member has been
replaced by an identical-looking impostor. (Invasion of the Body Snatchers; Day of the Triffids)
From: “Spiceophrenia”: a systematic overview
of “Spice”-related psychopathological issues
and a case report. Duccio Papanti, Fabrizio
Schifano, Giulia Botteon, et al. Hum.
Psychopharmacol Clin Exp 2013; 28: 379–389.
(A) CT angiogram showing a proximal left MCA clot (arrow). (B) MRI diffusion-
weighted imaging sequence showing large area of infarct in the left MCA
distribution. MCA 5 middle cerebral artery
Ischemic stroke after use of the synthetic marijuana 'spice'‘
Melissa J. Freeman, David Z. Rose, Martin A. Myers, et al. Neurology
published online November 8, 2013, p. 3., Figure 2.
Don’t Take Pharmacology
from Strangers
© Richard S. Blum, 2000
Thanks to Richard S. Blum, MD for permission to use his slides