Effects Of Synthetic Cannabinoids Research Articles

Effect of synthetic cannabinoids (JWH-018) on antibody response to HBV vaccination

Synthetic cannabinoids can affect the immune system and can cause some changes in immune response. The immune response to the Hepatit B vaccine is complex. Studies on hepatitis B vaccine antibody response and JWH-018 are extremely limited. The main aim of this study was to investigate the effect of JWH-018 on anti-HBs Ag changes before or after Hepatitis B vaccination. The study was performed on C57BL6 mice (n=25). Mice were divided into 3 groups. Control Group; it was immunized Engerix B at 3 times 3-week intervals. Group 1; JWH-018 (1 mg/kg) was administered once a week for 4 weeks. At the end of this period, Engerix B was immunized 3 times at 3-week intervals. Group 2; it was immunized 3 times at 3-weeks intervals with Engerix B. At the end of this period JWH-018 (1 mg/kg) was treated once a week for 4 weeks. Blood samples (3 times with an interval of 2 weeks) were collected at the end of drug and vaccine administration. It was calculated that the means obtained from the control group were lower than the other groups. The final measurement of the within-group was higher than other measures and was statistically significant (p=0,017). Statistical difference was measured in the first (p=0,018) and third measurements (p=0,005) of the between groups. A total of 5 mice from the experimental groups died at different stages of the study. In this study, the use of JWH-018 has been shown to be effective on the anti-HBs parameter. We think that our study is very valuable in terms of proving the relationship between JWH-018 and Anti-Hbs parameter. However, more data are needed to understand causation.

Neurotoxicity of Synthetic Cannabinoids Versus Cannabis in Adolescents

Using a multicenter case registry (Toxicology Investigators Consortium), researchers analyzed neuropsychiatric effects of synthetic cannabinoid (SC)

Neurocognition and Subjective Experience Following Acute Doses of the Synthetic Cannabinoid JWH-018: Responders Versus Nonresponders.

Introduction: Synthetic cannabinoid mixtures have been easily accessible for years, leading to the belief that these products were natural and harmless, which contributed to their popularity. Nevertheless, there are many reports of users ending up in hospital due to severe side effects such as tachycardia, aggression, and psychosis. Controlled studies on the effects of synthetic cannabinoids on human performance are lacking. In the present study, we assessed the safety pharmacology of the synthetic cannabinoid JWH-018 after acute administration.Methods: Seventeen healthy cannabis-experienced participants took part in this placebo-controlled, crossover study. Participants inhaled the vapor of JWH-018 (doses ranged between 2 and 6.2 mg) and were subsequently monitored for 12 h, during which vital signs, cognitive performance, and subjective experience were measured. Subjective high scores showed that there is a large variability in the subjective experience of participants. Therefore, a mixed analysis of variance, with “Responder” (i.e., subjective high score >2) as a between-subjects factor and “Drug” as a within-subjects factor (placebo and JWH-018), was used.Results: Serum concentrations of JWH-018 were significantly higher in the responders. Overall, JWH-018 increased heart rate within the first hour and significantly impaired critical tracking and memory performance. Responders to JWH-018 performed more poorly in tests measuring reaction time and showed increased levels of confusion, amnesia, dissociation, derealization, and depersonalization and increased drug liking after JWH-018.Conclusion: JWH-018 administration produced large variability in drug concentrations and subjective experience. Fluctuations in drug delivery probably contributed to the variation in response. JWH-018's impairing effects on cognition and subjective measures were mainly demonstrated in participants who experienced a subjective intoxication of the drug. Lack of control over drug delivery may increase the risk of overdosing in synthetic cannabinoid users.

The effects of synthetic cannabinoids (SCs) on brain structure and function

There is an increasing use of “Novel Psychoactive Substances” containing synthetic cannabinoids worldwide. Synthetic cannabinoids (SC) are highly addictive and cause severe adverse effects. The purpose of our study was to assess whether chronic use of SC alters brain volume and function. Fifteen SC chronic users and 15 healthy control participants undertook an MRI scan to assess brain volume and function while performing a working memory N-back task and a response-inhibition Go-No-Go task. SC users showed impaired performance on the N-back task but not on the Go-No-Go task. They also showed reduced total gray matter volume compared with control participants, as well as reduced gray matter volume in several cortical regions including the middle frontal gyrus, frontal orbital gyrus, inferior frontal gyrus, insula, anterior cingulate cortex and the precuneus. Moreover, SC users showed diminished brain activations in the precuneus, cuneus, lingual gyrus, hippocampus and cerebellum while performing the N-back task. No differences were found in brain activation while performing the response-inhibition task. This is the first study showing overall reduced grey matter volume and specific reduced grey matter volumes in chronic SC users. Furthermore, this study showed for the first time impairment in the neural brain mechanisms responsible for working memory in SC users. Our results of reduced grey matter density and diminished activation during a working memory task in SC users, may suggest vulnerability of the frontal-parietal network in chronic SC users.

Synthetic Cannabis Use in Israel: “Nice or Bad Guy—Spice”

An alarming increase in the use/abuse of synthetic psychoactive substances known as “designer drugs” or “legal highs” (“Nice Guy” in Israel) has caused the governments of many countries including the USA to pass legislation banning the sale, possession, and use of specific synthetic cathinones and cannabinoids. “New psychoactive substances” (NPS) pose a public health risk. Early research on synthetic cannabinoids done in the 1980s and 1990s describes benign outcomes. Research in vivo in animals supported the positive influence of synthetic cannabinoids as an antiemetic used to prevent vomiting and nausea. However, reports of emergency departments evidence the toxicity and side effects of synthetic cannabinoids. This situation calls for policy, law enforcement, and medical intervention to address this growing problem.

The effects of synthetic cannabinoids on executive function.

There is a growing use of novel psychoactive substances (NPSs) including synthetic cannabinoids. Synthetic cannabinoid products have effects similar to those of natural cannabis but the new synthetic cannabinoids are more potent and dangerous and their use has resulted in various adverse effects. The purpose of the study was to assess whether persistent use of synthetic cannabinoids is associating with impairments of executive function in chronic users. A total of 38 synthetic cannabinoids users, 43 recreational cannabis users, and 41 non-user subjects were studied in two centers in Hungary and Israel. Computerized cognitive function tests, the classical Stroop word-color task, n-back task, and a free-recall memory task were used. Synthetic cannabinoid users performed significantly worse than both recreational and non-cannabis users on the n-back task (less accuracy), the Stroop task (overall slow responses and less accuracy), and the long-term memory task (less word recall). Additionally, they have also shown higher ratings of depression and anxiety compared with both recreational and non-users groups. This study showed impairment of executive function in synthetic cannabinoid users compared with recreational users of cannabis and non-users. This may have major implications for our understanding of the long-term consequences of synthetic cannabinoid based drugs.

Expression of the cannabinoid CB1 receptor in Chinese hamster ovary cells: A specific cellular model to investigate the acute and chronic effects of synthetic cannabinoids

Expression of the cannabinoid CB1 receptor in Chinese hamster ovary cells: A specific cellular model to investigate the acute and chronic effects of synthetic cannabinoids

The Synthetic Cannabinoids Phenomenon.

« Spice » is generally used to describe the diverse types of herbal blends that encompass synthetic cannabinoids on the market. The emergence of smokable herbal products containing synthetic cannabinoids, which mimic the effects of cannabis, appears to become increasingly popular, in the new psychoactive substances landscape. In 2014, the existence of 134 different types of synthetic cannabinoids were reported by the European Union Early Warning System. These drugs are mainly sold online as an alternative to controlled and regulated psychoactive substances. They appear to have a life cycle of about 1-2 years before being replaced by a next wave of products. Legislation controlling these designer drugs has been introduced in many countries with the objective to limit the spread of existing drugs and control potential new analogs. The majority of the synthetic cannabinoids are full agonists at the CB1 receptor and do not contain tobacco or cannabis. They are becoming increasingly popular in adolescents, students and clubbers as an abused substance. Relatively high incidence of adverse effects associated with synthetic cannabinoids use has been documented in the literature. Numerous fatalities linked with their use and abuse have been reported. In this paper, we will review the available data regarding the use and effects of synthetic cannabinoids in humans in order to highlight their impact on public health. To reach this objective, a literature search was performed on two representative databases (Pubmed, Google Scholar), the Erowid Center website (a US non-profit educational organization that provides information about psychoactive plants and chemicals), and various governmental websites. The terms used for the database search were: "synthetic cannabinoids", "spice", "new psychoactive substances", and/or "substance use disorder", and/or "adverse effects", and/or "fatalities". The search was limited to years 2005 to 2016 due to emerging scientific literature at this period Health professionals should take into account that limited scientific evidence is available regarding the effect of synthetic cannabinoids use in humans. It thus urges to launch more systematic epidemiological studies, to develop and validate screening procedures, and to investigate the neurobiological and psychological correlates and risk factors associated to synthetic cannabinoids use and misuse.

Synthetic Cannabinoid-Induced Immunosuppression Augments Cerebellar Dysfunction in Tetanus-Toxin Treated Mice.

Synthetic cannabinoids are one of most abused new psychoactive substances. The recreational use of abused drug has aroused serious concerns about the consequences of these drugs on infection. However, the effects of synthetic cannabinoid on resistance to tetanus toxin are not fully understood yet. In the present study, we aimed to determine if the administration of synthetic cannabinoids increase the susceptibility to tetanus toxin-induced motor behavioral deficit and functional changes in cerebellar neurons in mice. Furthermore, we measured T lymphocytes marker levels, such as CD8 and CD4 which against tetanus toxin. JWH-210 administration decreased expression levels of T cell activators including cluster of differentiation (CD) 3ε, CD3γ, CD74p31, and CD74p41. In addition, we demonstrated that JWH-210 induced motor impairment and decrement of vesicle-associated membrane proteins 2 levels in the cerebellum of mice treated with tetanus toxin. Furthermore, cerebellar glutamatergic neuronal homeostasis was hampered by JWH-210 administration, as evidenced by increased glutamate concentration levels in the cerebellum. These results suggest that JWH-210 may increase the vulnerability to tetanus toxin via the regulation of immune function.

Effect of synthetic cannabinoids on spontaneous neuronal activity: Evaluation using Ca2+ spiking and multi-electrode arrays

Activation of cannabinoid receptor 1 (CB1) inhibits synaptic transmission in hippocampal neurons. The goal of this study was to evaluate the ability of benchmark and emerging synthetic cannabinoids to suppress neuronal activity in vitro using two complementary techniques, Ca2+ spiking and multi-electrode arrays (MEAs). Neuron culture and fluorescence imaging conditions were extensively optimized to provide maximum sensitivity for detection of suppression of neural activity by cannabinoids. The neuronal Ca2+ spiking frequency was significantly suppressed within 10min by the prototypic aminoalkylindole cannabinoid, WIN 55,212-2 (10µM). Suppression by WIN 55,212-2 was not improved by pharmacological intervention with signaling pathways known to interfere with CB1 signaling. The naphthoylindole CB1 agonist, JWH-018 suppressed Ca2+ spiking at a lower concentration (2.5µM), and the CB1 antagonist rimonabant (5µM), reversed this suppression. In the MEA assay, the ability of synthetic CB1 agonists to suppress spontaneous electrical activity of hippocampal neurons was evaluated over 80min sessions. All benchmark (WIN 55,212-2, HU-210, CP 55,940 and JWH-018) and emerging synthetic cannabinoids (XLR-11, JWH-250, 5F-PB-22, AB-PINACA and MAM-2201) suppressed neural activity at a concentration of 10µM; furthermore, several of these compounds also significantly suppressed activity at 1µM concentrations. Rimonabant partially reversed spiking suppression of 5F-PB-22 and, to a lesser extent, of MAM-2201, supporting CB1-mediated involvement, although the inactive WIN 55,212-3 also partially suppressed activity. Taken together, synthetic cannabinoid CB1-mediated suppression of neuronal activity was detected using Ca2+ spiking and MEAs.

Synthetic Ligands of Cannabinoid Receptors Affect Dauer Formation in the Nematode Caenorhabditis elegans.

Under adverse environmental conditions the nematode Caenorhabditis elegans can enter an alternate developmental stage called the dauer larva. To identify lipophilic signaling molecules that influence this process, we screened a library of bioactive lipids and found that AM251, an antagonist of the human cannabinoid (CB) receptor, suppresses dauer entry in daf-2 insulin receptor mutants. AM251 acted synergistically with glucose supplementation indicating that the metabolic status of the animal influenced the activity of this compound. Similarly, loss of function mutations in the energy-sensing AMP-activated kinase subunit, aak-2, enhanced the dauer-suppressing effects of AM251, while constitutive activation of aak-2 in neurons was sufficient to inhibit AM251 activity. Chemical epistasis experiments indicated that AM251 acts via G-protein signaling and requires the TGF-β ligand DAF-7, the insulin peptides DAF-28 and INS-6, and a functional ASI neuron to promote reproductive growth. AM251 also required the presence of the SER-5 serotonin receptor, but in vitro experiments suggest that this may not be via a direct interaction. Interestingly, we found that other antagonists of mammalian CB receptors also suppress dauer entry, while the nonselective CB receptor agonist, O-2545, not only inhibited the activity of AM251, but also was able to promote dauer entry when administered alone. Since worms do not have obvious orthologs of CB receptors, the effects of synthetic CBs on neuroendocrine signaling in C. elegans are likely to be mediated via another, as yet unknown, receptor mechanism. However, we cannot exclude the existence of a noncanonical CB receptor in C. elegans.

OP-089 Acute Effects of Synthetic Cannabinoid “Bonsai” on Ventricular Repolarization

OP-089 Acute Effects of Synthetic Cannabinoid “Bonsai” on Ventricular Repolarization

Synthetic Marijuana Causing Cardiac Arrest and Seizure in A 16-Year-Old Teenager and Review of the Literature

Background: Synthetic cannabinoid abuse has surged significantly in the past few years given the unmonitored online selling and ambiguous marketing. They are often wrongly perceived by teenagers and young adults as “harmless”. They are usually not detected on conventional urine drug toxicology screens. Here we describe a case of brief cardiac arrest within an hour of ingesting synthetic marijuana. Case presentation: A 16-year-old teenager had an asystolic cardiac arrest lasting for 10 seconds which was documented by cardio-respiratory monitoring in the Emergency Room, followed by a seizure episode within an hour of ingesting synthetic marijuana. He had a full recovery within a few hours. Conclusion: This adds to the growing evidence of cardiac effects of synthetic cannabinoids which include arrhythmias, cardiac arrest and myocardial infarction.

Effect of synthetic cannabinoids on blood–brain barrier

Introduction: In recent years, many adolescents have started using a popular legal alternative to marijuana called K2/Spice, made primarily of a blend of synthetic cannabinoids. Many of the effects of these compounds result from their action on the central nervous system (CNS), causing adverse effects and drug dependence among their users. The compound most commonly found in K2/Spice is the potent CB1 agonist JWH-018, and therefore most research efforts have focused on CB1 agonists. The role of other JWH compounds with potent affinity for CB2 has not been elucidated. JWH-015 and AM-630 are a cannabinoid CB2 agonist and antagonist, respectively. Little is known about their effects on the blood– brain barrier (BBB). Objectives: We hypothesized that JWH-015 and AM-360, which are both synthetic cannabinoids, will affect the CNS, specifically BBB integrity, permeability and gene expression. Materials and methods: The effects of JWH-015 and AM-630 were tested on an in vitro BBB model, which was constructed with human astrocytes and human brain microvascular endothelial cells. The integrity and function of the in vitro BBB was assessed by measuring transendothelial electrical resistance (TEER), FITC– dextran transport and JAM-2 expression. Results: The results showed the combination of synthetic cannabinoids JWH-015 and AM-630 caused a dose-dependent (1– 5μM) decrease in TEER values of the BBB. Conclusions: In our study, we observed that the combination of synthetic cannabinoids JWH-015 and AM-630 caused a decrease in TEER values of the BBB; therefore, comprising BBB integrity and increasing FITC– dextran transport and JAM-2 expression. These finding may further clarify the effects of synthetic cannabinoids and the role of CB2 on the CNS, specifically their degenerative or protective action on the BBB. Acknowledgements: Florida International University Biomedical Research Training Program Staff: Dr Juan Acuna MD, MSc, FACOG, Program Director; Dr Juan Lozano MD, MSc, Program Co-Director; Laura Boudon PhD, Associate Director, International Programs; Imam University Research Training Program Staff: Professor Khalid A Bin Abdurrahman MBChB, DPHC, ABFM, IAF (U of T), MHSc (MEd) Dean of College of Medicine; Sami Al-Daham, MD, Director of International Program; Amr Y Arkoubi MD, MBBS FRCSC Student’ s Supervisor. Financial support of this work was given in part by NIH grant: 1R01DA027049.

Use of Synthetic Cannabinoids in Patients With Psychotic Disorders: Case Series

An increasing number of synthetic cannabinoids have become available on the black market in recent years, and health professionals have seen a corresponding increase in use of these compounds among patients with psychiatric disorders. Unfortunately, there is almost no research available in the literature on this topic, and what little exists is based on case reports of individuals without psychiatric disorders. Synthetic cannabinoids are functionally similar to, but structurally different from, delta-9-tetrahydrocannabinol, the active principle in cannabis, and are problematic for many reasons. The psychotropic action of synthetic cannabinoids in patients with schizophrenia is unpredictable, with very diverse clinical presentations. These drugs can be much more potent than delta-9-tetrahydrocannabinol, they are readily available and difficult to detect. The gold standard for identification of synthetic cannabinoids is gas chromatography with mass spectrometry, but even this is difficult because new formulations of these designer drugs are constantly emerging. In this manuscript, we provide an overview and discussion of synthetic cannabinoids and present four cases of patients with synthetic cannabinoid intoxication who were hospitalized in our intensive psychiatric unit at the time of intoxication. All patients had a history of schizophrenia and had been hospitalized several times previously. While hospitalized, they smoked an unknown substance brought in by a visitor, which was then confirmed using gas chromatography with mass spectrometry to be the synthetic cannabinoid AM-2201. Our patients experienced predominantly psychiatric adverse clinical effects. We observed the appearance of new psychotic phenomena, without exacerbation of their previously known psychotic symptoms, as well as the occurrence or marked worsening of mood and anxiety symptoms. Despite several similar reactions, and even though they ingested the same exact substance, the clinical picture differed markedly between individual patients. We assume that the acute effects of synthetic cannabinoids in patients with schizophrenia would be different from those in persons without psychotic disorders. The reasons for this difference could be the actual symptomatology of the presenting disorder, the impact of psychopharmacotherapy, individual patient differences and probably many, as yet unknown, factors. The long-term consequences of synthetic cannabinoid use on preexisting psychotic disorders are unclear.

Behavioral effects of synthetic cannabinoids marketed as “spice”

negative urines, reduction in opioid craving, improvement inmental health functional quality of life, and no new safety concerns. Financial support: Funded by Alkermes, Inc. Drs. Gastfriend, Memisoglu and Silverman are employees of Alkermes, Inc. Dr. Earley is a paid consultant to Alkermes. Injectable extended-release naltrexone (Vivitrol®) was developed with support from National Institute onDrugAbuseGrant R43DA013531 andNational Institute on Alcohol Abuse and Alcoholism Grant N43AA001002.

The Synthetic Cannabinoid Withdrawal Syndrome

Little is known about the effects of synthetic cannabinoids. There has been only one previous report of a withdrawal syndrome from synthetic cannabinoids. We report two cases of a withdrawal syndrome from prolonged habitual use of synthetic cannabinoids. Withdrawal from delta-9-THC has been described as a syndrome of anxiety, myalgias, chills, and anorexia. Synthetic cannabinoids are potent than delta-9-THC and thus the withdrawal syndrome is similar but more severe; however the symptoms do not seem to improve with delta-9-THC. The differences in presentation could be due to the fact that synthetic products may contain several heterogeneous compounds, including amphetamine-like substances. The acute withdrawal syndrome appears to be characterized mainly by anxiety and tachycardia in the absence of any neurological findings or electrolyte disturbances. We describe two patients with symptoms consistent with withdrawal presumably due to synthetic cannabinoid use. The most appropriate treatment for such patients remains unknown, however benzodiazepines are a reasonable first line approach and quetiapine may have some efficacy.

Cómo responder al paciente con cáncer avanzado que nos plantea el uso de cannabis como tratamiento sintomático

ObjectiveTo contribute ideas to answer advanced cancer patients asking about the use of medicinal cannabis as a symptomatic treatment. MethodBased on a real example, we present a summary of the pharmacology of natural and synthetic cannabinoids, the evidence on its effectiveness as a symptomatic treatment in advanced cancer, and the patient's attitude and expectations raised by the medicinal use of cannabis. ResultThere are more than 60 different cannabinoids (the most relevant: delta-9-tetrahydrocannabinol) and other substances in cannabis. In our setting, patients who ask about the use of cannabis as a symptomatic treatment do not look for synthetic cannabinoids approved in other countries, but rather prefer herbal cannabis or its derivatives. They usually consume smoked cannabis (favoring the earlier onset of plasma levels) or, rarely, in infusion. Use of medicinal cannabis causes a wide variation in plasma concentrations of delta-9-tetrahydrocannabinol. There is evidence supporting a certain effect of synthetic cannabinoids in pain relief (also as an adjuvant), and as antiemetic for chemotherapy-induced nausea and vomiting in cancer patients. This evidence is based primarily on results of studies with limited methodological quality. There is insufficient evidence to assert its effectiveness in the treatment of anorexia. Side effects of moderate doses of synthetic cannabinoids or medicinal cannabis are mostly mild, as well as their psycho-neurological profile. The attitude and expectations of the patient, and the way to consume of medical cannabis may favor that part of its benefit may be due to a placebo effect. ConclusionsMedicinal cannabis does not seem as active as patients expect, or as toxic as many professionals suspect. To respond to the advanced cancer patient asking about their use as symptomatic treatment is advisable to avoid prejudice, to respect and to act with caution seeking the patient's symptomatic benefit.

Effects of synthetic cannabinoids on electroencephalogram power spectra in rats

Several synthetic cannabinoids have recently been distributed as psychoactive adulterants in many herbal products on the illegal drug market around the world. However, there is little information on pharmacology and toxicology of such compounds. Although Δ(9)-tetrahydrocannabinol (Δ(9)-THC), a psychoactive cannabinoid of marijuana, was reported to affect electroencephalograms (EEG) of rats, the effects of synthetic cannabinoids are unknown. We examined the pharmacological activities of three synthetic cannabinoids; cannabicyclohexanol (CCH), CP-47,497 and JWH-018; by analyzing EEG power spectra and locomotor activity after intraperitoneal administration to rats and compared them with those of Δ(9)-THC. The three compounds significantly increased the EEG power in the frequency range of 5.0-6.0 Hz for the first 3h, while Δ(9)-THC decreased the power spectra in the wide range of 7.0-20.0 Hz during the first hour. These results indicate that the effect of the three compounds on EEG is different from that of Δ(9)-THC. Additionally, CCH, CP-47,497 and JWH-018 significantly decreased the locomotor activity for 11.5h, 11h and 4.5h, respectively, after administration which was longer than that of Δ(9)-THC (3.5h). Furthermore, all three compounds significantly reduced the total amounts of locomotor activity during a 3-h, 6-h and 12-h period after injection, whereas no statistical difference was observed for the Δ(9)-THC injection. Among the three compounds, CCH and CP-47,497 exerted a longer duration of the change in the EEG power spectra and suppression of the locomotor activity than JWH-018.

Effect of Synthetic Cannabinoids on Elevated Intraocular Pressure

Two chemical derivatives of delta-1-tetrahydrocannabinol were evaluated in a randomized, double-masked study, administered as a single oral dose to a group of ocular hypertensive patients. One of the compounds (BW146Y) was found to have a significant intraocular pressure lowering effect that was independent of orthostatic blood pressure changes, although such changes did occur in some patients. The other compound (BW29Y) was ineffective in lowering intraocular pressure at the doses tested. Psychological and performance parameters were measured, and except for a time production test among the BW29Y group, these parameters were not significantly affected by the test drugs. Patients receiving both drugs experienced mild subjective side effects.