In “The Changing Face of Recreational Drug Use,” the title of this month’s Cerebrum
article, author Michael H. Baumann, Ph.D., a
staff scientist and facility head at the National Institute
on Drug Abuse, Intramural Research Program,
describes the complexity of the NPS problem, what is known
about the molecular mechanisms of action, and the pharmacological effects of
NPS. We asked him to elaborate on the article.
What was the impetus for establishing
the Designer Drug Research Unit at the NIDA?
establishment of the Drug Designer Research Unit (DDRU) was a direct response
to the rise in misuse and availability of these substances, which was right
around 2010-2011. I started becoming aware of the synthetic cathinone (i.e., “bath
salts”) and synthetic cannabinoid (i.e., “spice”) situations, and went to my section
chief and the scientific director at NIDA IRP to pitch the idea that I could
repurpose the laboratory to start studying these designer drugs. At the time,
there was little information available in terms of molecular mechanism or
pharmacology or toxicology of these new substances. My superiors were, and
still are, very supportive of the initiative to study designer drugs.
What classifies a drug as an NPS?
terms “designer drugs” and “new psychoactive substances” (NPS) are used to
describe newly-emerging synthetic drugs that are misused as alternatives to
more traditional illicit drugs of abuse. NPS are made in overseas laboratories,
and sold under false pretenses as non-drug products to reduce legal scrutiny. Compared
to more traditional drugs of abuse, NPS are cheap, easy to obtain, and not
detected by standard toxicology screens.
Why isn’t crystal meth mentioned in
though it is a synthetic drug, methamphetamine (meth) is not categorized as an
NPS because it has its own lengthy history. In terms of the manufacturing and
trafficking, for example, crystal meth is quite different than what we see with
NPS. Mexican cartels are involved with trafficking meth into the United States,
whereas NPS are made in Asian laboratories, bought in bulk off of the Internet,
and end up at various locations in Europe, Australia, the US, Japan and
elsewhere. The buyers will package and sell them to third-party vendors, such
as smoke shops, gas stations and in some cases, drug dealers on the street. Thus,
the way that NPS are marketed is quite different than what's going on with cocaine
or meth, drugs that have an entrenched, illicit trafficking history.
Out of the 540 different drugs
classified as NPS, which are best known?
though there have been hundreds of these drugs discovered, there really are
only a few that are popular at any given moment. For cathinone-like stimulants,
health professionals started seeing patients intoxicated with mephedrone,
methylone, and MDPV in 2010-11. That was the time of the “bath salts” craze.
But once emergency legislation went into effect to ban bath salts cathinones in
2011, there was an emergence of different “replacement” NPS. Information about
the prevalence of specific NPS in the recreational drug marketplace can be
obtained by examining data from DEA’s National Forensic Laboratory Information
System (NFLIS), which reports chemical analysis of the drug items confiscated
by local, state and Federal law enforcement.
Examining these data, one can see that most drugs come and go, but at
the moment, ethylone and alpha-PVP are two of the more prominent replacement drugs.
Ethylone, which is an analog of methylone, is being found in counterfeit
ecstasy pills. And alpha-PVP, which is
an analog of MDPV, is sold as “flakka” in the recreational drug marketplace in
Florida and other states. Alpha-PVP is causing a lot of problems with serious
overdoses and even fatalities.
regard to the cannabinoid-like compounds, JWH-018 and AM-2201 were some of the
early “spice” drugs during 2011-2012, whereas today AB-PINACA and AB-FUBINACA
are being confiscated on the streets.
Most of the NFLIS data available to the public is at least six
months-old, and it’s hard to know what we will be talking about in six months
or a year from now.
Has the movement towards the legalization of marijuana led to
more drug abuse?
I don't have a firm answer, but I’d say that there is a general sentiment
misconstrued among young people that marijuana is okay because it’s been
legalized in certain states. So the
logic is that another type of marijuana, like synthetic cannabinoids, might
also be okay and safe to use. But this logic is obviously flawed and
incorrect. I would submit that whether
marijuana is legal or not, you’re still going to have a problem with synthetic
cannabinoids because one of the factors driving use in certain segments of the
population is that synthetic cannabinoids (and other synthetic drugs) can be
used without detection. Military personnel, athletes, and especially parolees
and probationers, are going to use synthetic cannabinoids instead of regular
marijuana to avoid detection by standard drug tests. So the element of secrecy is
driving use in certain populations.
Is there any specific demographic that is drawn to NPS?
anyone can get them. One issue I point out in the article is that while young
people can’t buy alcohol and cigarettes in stores, nothing stops them from
going on the Internet and getting NPS.
How addictive are NPS, as compared to heroin and cocaine?
would depend on the class of drug. Certainly, a potent opiate that binds to the
mu opioid receptor like heroin (e.g., synthetic fentanyl derivatives) would be
very addictive. Similarly, drugs that interact potently with the dopamine
transporter like methamphetamine and cocaine (e.g., MDPV and alpha-PVP) would
be very addictive drugs, where the propensity for binge misuse often leads to dangerous
symptoms requiring emergency medical care.
You point out that NPS are not
detectable through toxicology screens. Is that something the NIDA or anyone
else is close to rectifying?
There are many forensic toxicologists who are working on this problem right
now. We need forensic assays to detect NPS in biological specimens. The
standard toxicology screen is an immunoassay that is sensitive to a panel of the
more traditional drugs of abuse like cocaine, heroin and methamphetamine. All of
these newer drugs, because they’re coming fast and furious, would add a
significant number of different drugs to the standard toxicology screen. There
are companies trying to develop broad spectrum immunoassays to detect designer
drugs. However, because the drug landscape is changing so quickly, it becomes
difficult to get detection of all the relevant substances in a single assay.
going on around the country is that various labs are developing more
sophisticated analyses, such as LC/MS-MS (tandem mass spectroscopy) methods, to
be able to detect NPS and their metabolites. In fact, Dr. Marilyn Huestis and
her colleagues at the NIDA IRP are important collaborators with the DDRU, and
are leading the way in new assay development.
in most clinical or hospital settings, such sophisticated instrumentation and
methods are not available. We are definitely playing catch up in this regard.
that said, scientists are making a lot of progress on developing assays. It's especially
complicated for the synthetic cannabinoids—as soon as these substances are
smoked—the parent compound is rapidly transformed by liver mechanisms to a
variety of metabolites found throughout the body. When you look for the parent
compound in urine, it won’t be present. So,
a major challenge is determining the metabolites of given drug once it enters
the body, because we don't have much information in humans (there are no
controlled clinical studies in humans). The only information that we have from humans
is from hospital admissions, for example.
You write that
controlling NPS abuse will require international cooperation. Has there been
any recent progress on that front, or are there any movement towards increasing
enforcement on the Internet or on a global level?
I think it will be difficult to control
Internet commerce. A more reasonable way of stemming the tide
of drugs from Asian laboratories is to have a coordinated effort amongst all of the
governments involved on a global scale, and get assurances from those countries
that are making these products that they’ll stop people from doing it.
Of course, this is a sensitive
political issue that has to be addressed through proper diplomatic channels. Nevertheless,
there is some indication that the Chinese government has made many NPS illegal with
recent legislation, which means that the companies formerly making those drugs
will no longer be able to legally do it. Such legislation could have profound
implications for the availability of these drugs.