Synthetic Cannabinoids (Toxicology)

Synthetic cannabinoids (synthetic cannabimimetics) are synthetic substances pharmacologically acting as agonists of cannabinoid receptors. These are substances originally developed as tools to study the endocannabinoid system  or substances intended for standard pharmaceutical research. Synthetic cannabinoids emerged as a response to legislative restrictions on marijuana. As a new substance, in many countries they bypass the legislative regulation of addictive and psychoactive substances.

Applications
Synthetic cannabinoids are usually applied to a plant carrier, which is then consumed in the usual way for marijuana, i.e. by smoking. Since these are substances with a higher affinity to receptors and a higher mimetic activity, the effect of the substances is more powerful.

The problem for toxicological analysis is that many "commercial" brands are generic in the sense that they just mean an herbal carrier with a synthetic cannabinoid. The world's most famous label is Spice  or  K2. A regionally significant drug is mocarz  (in Polish, it is usually translated into Czech as močnář), which has recently spread mainly in Poland. 3-(2-Chlorophenylacetyl)indole (JWH-203) was identified as the active ingredient of this drug.

Chemical properties
Chemically, synthetic cannabinoids are not one group of substances, several groups can be distinguished according to the basic structure. Derivatives of indole 3-carbonyl represent the largest group of synthetic cannabinoids, including JWH-203 identified as the active component of mocarza. Other chemical groups of synthetic cannabinoids are 3-carbonyl derivatives of pyrrole and indazole, 3-carbonylamide and 3-carbonyl ester derivatives of indole or indazole.

Groups of synthetic cannabinoids are also referred to by the initials of the scientists who synthesized the respective compound. E.g. the abbreviation JWH represents the initials of John William Huffman, Emeritus Professor of Organic Chemistry at Clemson University, the abbreviation AM represents the initials of Alexandros Makriyannis, a professor at Northeastern University.

Importantly from the point of view of toxicological analysis, synthetic cannabinoids are chemically different from natural cannabinoids, so analytical tests may not be reliable:


 * Duquenois's Levin test fails.
 * Van Urk's test fails.
 * 2,4-dinitrophenylhydrazine reacts with some synthetic cannabinoids, incl. those that are applied on a plant carrier, resulting in a yellow to orange coloration of the solution.
 * Marquis' reagent reacts with some synthetic cannabinoids, in particular it reacts with the JHW series cannabinoids.
 * The Dragendorff reaction is positive for the JWH series, but the reaction is less sensitive.
 * Fast blue BB reacts with cyclophenols.
 * Iodoplatinate is used as a detection reagent after separation by thin layer chromatography. The disadvantage of chromatography is that the detection of a mixture of synthetic substances is difficult.
 * ELISA is available for some drugs.
 * Immunochemical kits for the detection of synthetic cannabinoids in urine are available, but they tend to detect older drugs, they may not detect new ones.
 * Gas chromatography-mass spectrometry (GC-MS) detection is sensitive and will pick up new substances, but there is a risk of false positives because the interpretation of the spectrum is quite difficult.
 * Detection using liquid chromatography and mass spectroscopy (LC-MS) is more of a research topic.

Drug action
The effect is similar to cannabinoids from natural hemp, but especially the new substances show a stronger affinity and stronger mimetic activity on CB1 and often CB2 receptors. In addition to more pronounced psychotic manifestations, a significant sympathomimetic effect also appears.

An overdosed person may be somnolent or euphoric, but will usually be agitated and aggressive, aggressiveness may be expressed especially verbally. The speech of an intoxicated person may be incoherent. Memory disturbances, hallucinations and delusions appear, especially paranoid delusions. Nausea and vomiting are common.

Chest pain may appear, the intoxicated person may complain of palpitations. Arterial hypertension is common. This finding may also have a correlate in the form of ST elevation on the ECG and an increase in cardiac markers in the plasma. The basis of these changes is probably the spasm of the coronary arteries.

Proteinuria and oliguria accompanied by an increase in plasma creatinine may occur. Changes in the kidneys can result in tubular necrosis and thus in acute renal failure.

Muscle weakness and tremors may occur. Convulsions that could result in status epilepticus have been described. Cases with dyspnoea, conjunctival injection or headache were also described.

Other difficulties may also appear. For example, a case report of the association of intoxication with synthetic cannabinoids with acute liver failure  was published.

Therapy
Therapy, if necessary, is primarily symptomatic. If blood pressure reaches critical values, it is not advisable to reduce it with beta blockers, it is more appropriate to induce peripheral vasodilation. If convulsions or status epilepticus occur, benzodiazepines are the drug of choice.

The effect of synthetic cannabinoids is usually rather short-lived, so in most cases of intoxication, shorter monitoring and support is sufficient.

Related articles

 * Substance abuse
 * Cannabinoids
 * Disorders induced by the use of cannabinoids
 * Drug addiction and illegal production and possession of narcotics

Literature

 * NAMERA, A., M. KAWAMURA a A. NAKAMOTO, et al. Comprehensive review of the detection methods for synthetic cannabinoids and cathinones.  Forensic Toxicol.  2015, roč. ., vol. ., s. ., sv. In Press. ISSN 1860-8973. DOI: 10.1007/s11419-015-0270-0.


 * LIECHTI, M.E.. Novel psychoactive substances (designer drugs): overview and pharmacology of modulators of monoamine signalling.  Swiss Med Wkly [online] .  2015, roč. 145, s. w14043, dostupné také z < http://www.smw.ch/content/smw-2015-14043/ >. ISSN 1424-7860.


 * BREWER, T.L. a M. COLLINS. A review of clinical manifestations in adolescent and young adults after use of synthetic cannabinoids.  J Spec Pediatr Nurs [online] .  2014, vol. 19, no. 2, s. 119-26, dostupné také z < https://www.ncbi.nlm.nih.gov/pubmed/24320158 >. ISSN 1744-6155.


 * SPENGER, E. a D. LABRECQUE.  ACG 2014 Annual Scientific Meeting Abstracts : Program No. P923  [online]. American College of Gastroenterology, ©2044. [cit. 14.7.2015]. < http://eventscribe.com/2014/acg/TwitterPoster.asp?PosterID=30948 >.