Synthetic cannabinoid receptor
agonists (also called SCRAs or synthetic cannabinoids) are laboratory
developed chemicals that bind to the cannabinoid receptors 1 and 2 (CB1
and CB2) in the body. CB1 receptors are primarily located
in the central nervous system (the brain and spinal cord) and are responsible
for mediating the psychoactive effects of cannabis. The CB2
receptors are primarily located in the peripheral nervous system, as well as
the spleen and immune system, and are thought to be involved in pain perception
mediation and immunosuppression. While delta-9-tetrahydrocannabinol (THC), the
primary psychoactive component found in marijuana, is a partial agonist of both
the CB1 and CB2 receptors, SCRAs are considered
to act as full agonists of the same receptors.
Are
these substances the same as marijuana?
No. The media loves to
use the words synthetic marijuana or synthetic weed or synthetic pot to describe SCRA containing
products. This description could not be further from reality. SCRAs and
related products are not marijuana.
From where did these
compounds originate?
Many
compounds have originated in academic research on new drug targets and the
cannabinoid receptor systems. The JWH series (JWH-018, JWH-019, JWH-122, etc.)
of SCRAs were developed at Clemson University under Dr. John W. Huffman.
AM-2201 was developed at Northeastern University under Alexandros Makriyannis.
Another SCRA, UR-144, was developed by Abbott Labs. XLR-11, a 5-fluorinated
derivative of UR-144, was covered under an Abbott Labs patent, but never
synthesized. The indazole carboxamide ADB-FUBINACA was synthesized by Pfizer as
a possible therapeutic drug. Some compounds on the market today have no formal
academic or industry history and are the product of clandestine chemists using
rational drug design.
Are these chemicals considered
“controlled substances” in the USA?
In the
USA, SCRAs have been sold as ingredients in herbal incense, herbal
potpourri, or smoking blends since approximately 2009 and have become popular
as a cannabis alternative. The powders are also available via the Internet.
Throughout the last several years in the USA, various waves of legislation have
been passed by the Federal government classifying several synthetic
cannabinoids as Schedule I controlled substances. Schedule I controlled
substances are those substances that are considered to have a high potential
for abuse, a potential for severe psychological or physical dependence, and
have no currently accepted medical use in the USA. These substances are illegal
to possess, manufacture, and distribute. As this legislation is enacted,
manufacturers and vendors of these substances and resulting mass-produced
retail products vary the active ingredient(s) to now uncontrolled (and
quasi-legal) substances. Currently there are twenty four (24) synthetic
cannabinoids explicitly controlled by the Federal government as Schedule I
controlled substances.
These are:
5F-PB-22, AB-CHMINACA,
AB-FUBINACA, AB-PINACA, ADB-PINACA, AKB48/APINACA, AM694, AM2201, CP-47,497,
CP-47,497-C8 homologue, JWH-018/AM678, JWH-019, JWH-073, JWH-081, JWH-122,
JWH-200, JWH-203, JWH-398, PB-22, RCS-4/SR-19, RCS-8/SR-18, THJ-2201, UR-144,
and XLR-11
Each state in the USA has its own
controlled substance laws. As there is considerable variation in inter-state laws
– some states have blanket bans on chemical structure classes and other states
only explicitly list substances by name while other states use a combinatorial
approach – please consult those specific laws for a list of scheduled
substances.
How are these products made?
Common plant material, such as
marshmallow leaf, mullein, or damiana can be easily purchased over the internet
in bulk and used as the base for the herbal incense product. The drug material
can also be purchased over the Internet and is then dissolved in acetone or
high proof ethanol and sprayed on the plant material. The plant material is
dried and packaged for distribution. The laboratories in which these products
are made do not possess stringent quality assurance/quality control (QA/QC)
policies, so there tends to be much cross contamination of product as well as
intra-product variation in actual synthetic cannabinoids used. Also, due to the
lack of QA/QC procedures, there may be ‘hot spots’ of drug in certain section
of the plant material, which essentially means that the drug is not uniformly
applied to the substrate leading to extreme variation in dosages across a batch
of product.
How are these substances or products consumed?
The plant material products can
be rolled up in a cigarette or joint and smoked like tobacco or marijuana. The
chemical powder can also be smoked. SCRAs are also available in liquid form for
vaping via electronic cigarettes (e-cigarettes).
What are some commonly reported effects of these
substances?
Common cognitive and psychomotor
effects attributed to SCRAs include poor coordination, instability, slowed
movements, sedation, sway, balance issues, slowed or slurred speech, agitation,
irritability, delusions, paranoia, hallucinations, and psychosis. Other adverse
effects that have been observed include nausea, vomiting, tachycardia,
hypertension, hyperthermia, and acute kidney injury. Several fatalities have
occurred after use of these substances. As with any drug, effects seem to be
very dose-dependent. Lower doses will elicit the more common effects while
larger doses or repeated dosing will lead to the more exaggerated adverse
effects.
What are a forensic toxicologist’s thoughts on
SCRAs?
In the laboratory, we’ve been
dealing with synthetic cannabinoids for approximately the last 6 years. In
2009-2010, there were only 1-2 synthetic cannabinoids detected
in casework. Via different forces on the market (in my opinion, not the
only factor, but primarily legislation) the market exploded in sheer number of
compounds and continues to change with the ever-evolving controlled substance
laws. The USA has legislated itself into a public health nightmare. By
continually outlawing substances, we have allowed compounds with completely
unknown pharmacological and toxicological profile to find their way to the
grey-market. We are only seeing the beginnings of this nightmare through mass
hospitalizations and outbreaks of illnesses (and a noted increase in phone
calls to poison centers) after use of synthetic cannabinoid-containing
products. The vast majority of people using these substances and products are
consuming substances of unknown
identity with unknown pharmacological
and toxicological profiles in unknown
combinations at unknown dosages. This
is reckless behavior. This is dangerous behavior. It will result in serious
adverse health effects for the individual.
The chemical diversity in
structure of these compounds is amazing. Take a bit of substance A and mix it
with this bit from substance B and add it all together with this group from
substance C. Voila! We have new alphabet soup synthetic cannabinoid compound D!
I’ve coined the phrase “diverse chemical grab bag o’ death” to describe these
substances. We know very little of the true acute effects of individual
synthetic cannabinoids. We know nothing of the long-term or chronic effects of
synthetic cannabinoid use (and we will not for quite some time). We do not know
if they act on other receptors or mediate other effects downstream. It is
thought that they do not, but who knows. And therein is the important part of
this - we know nothing about these compounds. Nothing. And that is what makes
them dangerous.
