Analytical Chemistry , 83 , — Kennedy P. Endres G. Uzieblo A. Dobrowolski P. ElSohly M. Gul W. Elsohly K. Murphy T. Madgula V. Khan S. Journal of Analytical Toxicology , 35 , — Hutter M. Broecker S. Kneisel S. Auwarter V. Journal of Mass Spectrometry , 47 , 54 — Sobolevsky T. Prasolov I. Rodchenkov G. Forensic Science International , , — Wohlfarth A. Scheidweiler K.
Chen X. Liu H. Huestis M. Analytical Chemistry , 85 , — Journal of Chromatography A , , — Lee S. Forensic Science International , , 13 — Yanes E. Lovett D. Journal of Chromatography. Simoes S. Silva I.
Ajenjo A. Dias M. Warner J. Henman M. Ferguson W. Hall A. Matuszewski B. Constanzer M. Chavez-Eng C. Analytical Chemistry , 75 , — Hegstad S. Hermansson S. Betner I. Spigset O. Falch B. Poklis J. Amira D. Wise L. Wiebelhaus J. Haggerty B. Poklis A. Forensic Science International , , 91 — Handbook of Experimental Pharmacology , , — Westin A.
Burchardt O. Cone E. Journal of Analytical Toxicology , 22 , — Smith M. Barnes A. Journal of Analytical Toxicology , 33 , — Aarstad K. Since vehicle administration did not change catalepsy scores over the course of treatment, we compared the effects of JWH treatment across days to the effects of vehicle treatment on day 1.
Using this analysis, JWH increased catalepsy scores compared to vehicle Kruskal—Wallis statistic Rats received 0. Similar non-significant effects between pretreatment groups were observed at day 7. DOI did not significantly affect core body temperature in rats pretreated with JWH or vehicle at either test day data not shown.
Summed scores for wet dog shakes and back muscle crawls skin jerks induced by a subcutaneous challenge injection of 0. Behavioral scores were recorded at 0, 0. A separate cohort of rats was given 0. Summed scores for serotonin syndrome behaviors and mean temperature recordings induced by a subcutaneous challenge injection of 0.
Behavioral scores and core temperatures were recorded at 0, 0. Post hoc tests revealed that temperature was significantly decreased in the JWH group compared to the vehicle group at 1.
Time-course of core body temperature changes induced by a subcutaneous challenge injection of 0. Temperatures were recorded at 0, 0. The psychiatric literature supports a strong relationship between heavy cannabis use and risk for subsequent psychosis and schizophrenia In addition, misuse of synthetic cannabinoids such as JWH and its analogs is associated with induction of more severe psychotic symptoms when compared to the effects of marijuana 26 , The aim of the present study was to use the popular synthetic cannabinoid JWH to further explore the relationship between repeated cannabinoid exposure and serotonergic dysregulation.
JWH is a potent non-selective cannabinoid receptor agonist that was found in the first generation of spice products 1 , 2. The present experiments yielded three primary findings. First, in contrast to the results of others [e. Second, we found a modest and significant enhancement of sensitivity to behavioral and hypothermic effects induced by 8-OH-DPAT in rats exposed to repeated injections of JWH Typical behavioral responses to DOI administration in rats are wet dog shakes analogous to the head twitch response in mice and back muscle contractions, also known as skin jerks 21 — These responses are accepted as specific indicators of 5-HT 2A receptor activation since the effects are blocked by selective 5-HT 2A receptor antagonists.
We found no significant difference in the number of wet dog shakes or skin jerks induced by DOI between the cannabinoid-treated and vehicle-treated groups at either time point. Our findings differ from those of Hill et al. It is noteworthy that we observed trends for augmented wet dog shakes and attenuated skin jerks in rats exposed to JWH, but these effects did not reach significance, perhaps due to variability in the behavioral data.
We also administered a submaximal dose of 0. Hill et al. This hypothesis was later supported by the work of Franklin et al. It is well known that HU displays a much longer time course of action when compared to other synthetic cannabinoids, including JWH, and may bind pseudo-irreversibly to the CB 1 receptor. Thus, the discrepancies between our results and those of Hill et al. We found a modest yet significant increase in the behavioral and hypothermic effects induced by 8-OH-DPAT in rats receiving repeated JWH treatments when compared to those receiving repeated vehicle treatments.
In a previous study, Hill et al. Both hypothermia and corticosterone release are presumably mediated by 5-HT 1A receptors in the brain 31 , thus Hill et al. It seems possible that discrepancies between our results and those of Hill et al. On the other hand, Zavitsanou et al.
Our data demonstrating an increase in 5-HT 1A receptor sensitivity after exposure to JWH is a unique finding, and its relationship to the development of psychiatric symptoms following cannabinoid exposure warrants further study.
Future research should determine whether 5-HT 1A upregulation occurs after repeated exposure to other synthetic cannabinoids. Importantly, and in contrast to existing findings using other cannabinoid compounds, our data show that repeated exposure to JWH does not induce robust alterations in 5-HT 2A receptor responsiveness, but increases 5-HT 1A responsiveness. In addition to assessing changes in serotonergic activity after cannabinoid exposure, one of the secondary aims of our study was to examine pharmacological responses to repeated JWH injections.
Rats in our study had implantable temperature transponders to facilitate the non-invasive measurement of body temperature. The present data showing acute decreases in body temperature after JWH administration in rats are consistent with previous findings from our laboratory and others, which show dose-related hypothermic effects of JWH as assessed by radiotelemetry or rectal probes to measure core temperatures 33 — As the repeated injection procedure progressed in our study, rats began to develop tolerance to both the hypothermic and cataleptic effects produced by JWH By day 5 of repeated treatments, the effects of JWH became submaximal at all time points, and continued to decrease in the two remaining days.
By day 7 of repeated treatments, the temperature and cataleptic effects JWH were not significantly different from vehicle-treated animals. Previous studies in mice have shown that repeated daily injections of THC or synthetic cannabinoids produce behavioral tolerance due to downregulation and desensitization of CB 1 receptors Likewise, acute JWH is reported to induce downregulation of CB 1 receptors in cultured neurons by a mechanism involving rapid receptor internalization The experiments of Tai et al.
The apparently contradictory findings between our results and those of Tai et al. Tai et al. The development of tolerance to cannabis is well documented, and the demonstration of tolerance to JWH could have important clinical implications 40 , Dose escalation in human THC users is often observed as a means to overcome cannabis tolerance, but this phenomenon likely will not cause acute bodily harm.
By contrast, dose escalation with JWH or other potent synthetic cannabinoids could be more dangerous. Typical adverse effects arising from synthetic cannabinoid use are tachycardia, agitation, and nausea; more serious adverse events include seizures, acute kidney injury, new onset psychosis, severe cardiac crisis, and death 27 , McRae-Clark , Abigail G.
Vandrey , Frances R. Levin , Roger D. Mooney , Louise Haynes , Gregory S. Brigham , Steve Sparenborg , Albert L. Hasson , Kevin M. Contemporary Clinical Trials , 39 2 , Takematsu , R.
Hoffman , L. Nelson , J. Schechter , J. Moran , S. A case of acute cerebral ischemia following inhalation of a synthetic cannabinoid. Clinical Toxicology , 52 9 , Tang , C. Ching , Caroline Y. Science of The Total Environment , , Temerdashev , I. Evolution of new narcotic substances and methods of their determination. Journal of Analytical Chemistry , 69 9 , Klette , Marilyn A.
Evaluation of a homogenous enzyme immunoassay for the detection of synthetic cannabinoids in urine. Bick , Jason H. Szostek , Thomas F.
Mayo Clinic Proceedings , 89 8 , Recent developments in urinalysis of metabolites of new psychoactive substances using LC—MS. Bioanalysis , 6 15 , Biomedical Chromatography , 28 6 , Analytical and Bioanalytical Chemistry , 15 , Metabolism of RCS-8, a synthetic cannabinoid with cyclohexyl structure, in human hepatocytes by high-resolution MS.
Bioanalysis , 6 9 , Characterization of in vitro metabolites of JWH, JWH and their 4-methyl derivatives, markers of the abuse of these synthetic cannabinoids. International Journal of Legal Medicine , 2 , Nelson , Sean M. Bryant , Steven E. Emerging drugs of abuse. Disease-a-Month , 60 3 , Zawilska , Jakub Wojcieszak.
The International Journal of Neuropsychopharmacology , 17 03 , Emerging Drugs of Abuse. Emergency Medicine Clinics of North America , 32 1 , Life Sciences , 97 1 , Fantegrossi , Jeffery H. Brents , Paul L. Drug Metabolism Reviews , 46 1 , Simultaneous quantification of 20 synthetic cannabinoids and 21 metabolites, and semi-quantification of 12 alkyl hydroxy metabolites in human urine by liquid chromatography—tandem mass spectrometry.
Journal of Chromatography A , , Thornton , Carl R. Bath Salts and Other Emerging Toxins. Pediatric Emergency Care , 30 1 , Screening for synthetic cannabinoids in hair by using LC-QTOF MS: A new and powerful approach to study the penetration of these new psychoactive substances in the population.
Medicine, Science and the Law , 54 1 , Analytical and Bioanalytical Chemistry , 30 , Analytical and Bioanalytical Chemistry , 26 , Acute intoxication by synthetic cannabinoids - Four case reports. Drug Testing and Analysis , 5 , Bioanalysis , 5 18 , Analysis of 30 synthetic cannabinoids in oral fluid using liquid chromatography-electrospray ionization tandem mass spectrometry. Drug Testing and Analysis , 5 8 , Journal of Separation Science , 36 16 , Spicing things up: synthetic cannabinoids.
Psychopharmacology , 4 , Similarly, acute kidney injury resulting in hospitalization and dialysis have been connected to these synthetics. One study compared the level of impairment for drivers who were arrested for intoxicated driving. One group had smoked synthetic cannabinoids and those in the other group had used marijuana. The study found a significant increase in confusion, disorientation, and incoherence in the synthetic marijuana group. Slurred speech, a side effect not normally associated with natural cannabis use, was also reported among the people who had taken synthetic cannabinoids.
Beyond the short-term effects mentioned, an increase in blood pressure, as well as seizures, tremors, and anxiety, have been noted in people who have used synthetic marijuana. Whether these observed symptoms will have lasting effects, particularly on adolescents and young adults, is not yet known. Of course, smoking any substance could have negative effects on the lungs. There were also cases in which a version of synthetic marijuana was laced with rat poison, causing uncontrolled bleeding in hundreds of people and killing several others who ingested the tainted products.
If you or a loved one has used synthetic marijuana and begin experiencing severe, unexplained bleeding or bruising, call or asked a loved one to take you to the hospital immediately. These are all signs of contaminated cannabinoid products. If you are a parent of a young adult, it pays to know the behaviors and physical effects of using fake weed. While exhibiting one or two of these signs might not mean that your child is using, they are all strong indicators of drug use and should be taken seriously.
Physical effects:. Contrary to common belief, herbal bud is not "natural marijuana. Synthetic marijuana is also far more potent, containing THC analogs or synthetic cannabinoids that can be up to times more potent than THC found in marijuana.
Often, additives, toxic impurities, and other types of drugs are also found in fake weed products. If you regularly use synthetic cannabinoids, you can also become both physically and psychologically dependent. This means if you stop abruptly, you'll likely experience withdrawal symptoms. Since the chemical composition of fake weed is unknown and can change from batch to batch, tolerance, dependence, and withdrawal may also vary.
How long synthetic cannabinoids stay in your system depends on several factors, including the type, how it is administered i. Since these synthetic drugs don't trigger a positive result on most standard urine drug tests, many people turn to these drugs in an attempt to avoid positive drug screens for employment, rehab, or legal reasons. Long-term, regular use of synthetic cannabinoids can lead to addiction.
If you have a history of mental illness or a substance use disorder, the risk of addiction is even greater. In addition to building up a tolerance and experiencing symptoms of withdrawal, other signs of synthetic cannabinoid addiction can include:. Symptoms of synthetic weed withdrawal can range from mild to severe, depending on how frequent and how long you have been using, and include the following:. If you suspect that someone you love is using synthetic marijuana, the most important thing you can do is spend time with them, communicate the dangers of fake weed, and watch for any signs of use.
While behavioral therapies and medications have yet to be specifically tested for the treatment of synthetic cannabinoid addiction, a healthcare professional can work with you and your loved one to safely detox from the drug as well as identify and treat any co-occurring mental illness.
For more mental health resources, see our National Helpline Database. Learn the best ways to manage stress and negativity in your life. National Institutes of Health. Updated February US Senate. Statement of Joseph T. September
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