Why is jwh bad for you

This behavioral effect resembles the psychostimulant action of cocaine 18 — 22 and amphetamine 23 — Moreover, previous in vivo microdialysis studies demonstrated that JWH, at the dose of 0. Similar pharmacological properties were displayed by subsequent chemical generations of SCBs 7 , 10 , This study, by combining different experimental approaches, such as in vitro binding , in vivo behavioral tests, imaging and microdialysis and ex vivo synaptosome ones, aimed at clarifying how these SCBs modulate dopaminergic signaling and whether these putative effects could be relevant for their locomotion facilitating properties.

In particular, the effects of JWH and AKB48 have been compared to those induced by cocaine and amphetamine, two psychostimulant drugs affecting the dopamine transporter DAT in a different way. Indeed, while cocaine acts as a DAT blocker by directly binding to DAT and, thus, preventing the translocation of DA, amphetamine competes with DA for binding to the empty transporter, leading to the reverse transport efflux of DA from the intracellular compartment to the synaptic cleft, thus exerting indirect effects [e.

Moreover, adequate measures were taken to minimize the number of animals used and their pain and discomfort. For in vivo behavioral studies, all compounds JWH, AKB48, amphetamine sulfate, cocaine hydrochloride, AM, SCH, and haloperidol were initially dissolved in absolute ethanol and Tween 80 and then diluted to the final volume with saline 0.

The used doses of JWH 0. The used concentrations of JWH, AKB48, cocaine, and amphetamine were chosen on the basis of previous studies 7 , 17 , 28 , The spontaneous locomotor activity was measured by using the ANY-maze video tracking system Ugo Basile, application version 4. Four mice were monitored in parallel in each experiment. All experiments were performed between a. A control group i. Subtraction of dark noise contribution and flat field corrections was accomplished to obtain final images.

These ROIs were used as a template. To avoid the variability of the slice selection and to gain statistical power, the entire striatum volume for the analysis was used. The landmarks for positioning were the intra-orbital glands, striatum, and the borders of the brain. Harlan Italy; S.

On the day of the experiment, the animal was euthanized, the brain was rapidly removed, and both striata isolated. Thereafter, a crude synaptosomal P2 fraction was prepared as follows: the striata were suspended in ice-cold buffered sucrose solution 0. After synaptosomal preparation, 0. At the end of the experiment, the radioactivity of the samples and filters was determined by liquid scintillation spectrometry LS Beckman.

In view of the results obtained, in a separate set of experiments, [ 3 H]-DA uptake was also evaluated. Thereafter, 0.

After this period, the reaction was stopped by filtration through microporus nylon filters 0. The acute i. Data are expressed as meters total distance traveled and as seconds immobility time; time in the peripheral and central zone.

The facilitation of spontaneous locomotion induced by JWH 0. ROIs for the striatum. Means and SDs are shown. The effect of the treatments on [ 3 H]-DA uptake is expressed as percent of control values, i. The present multidisciplinary study, for the first time, directly compared the effects of JWH and AKB48, with those of cocaine and amphetamine, to provide further insights on the mechanism of action possibly underlying the psychomotor stimulant effects of SCBs. The behavioral studies, first, showed that JWH 0.

The SCBs-induced motor facilitation probably occurs in a narrow range of doses since SCBs mainly inhibited both spontaneous and stimulated motor activity in CD-1 mice 6 , 7 , 10 , 41 , Motor impairment is one of the main behavioral effects observed after systemic administration of cannabinoid receptor agonists 43 , 44 , and it has been associated with the stimulation of cerebellum and basal ganglia CB 1 receptors 43 , 45 , However, preclinical studies reported that cannabinoid receptor agonists time- and dose-dependently modulated rodent spontaneous locomotion in a biphasic fashion, with a facilitation and an inhibition at low and high doses, respectively.

Although the acute administration of either JWH 0. These diverse profiles are probably due to the different doses of JWH 0. It seems likely that the steric hindrance of the adamantly group of AKB48 delays the passage through the blood—brain barrier or limits a quick bond to CB 1 receptors. Normally, rodents tend to move in the perimeter of an arena i. As from an ethological point of view, a mouse that spends more time in an open space is less concerned about being attacked by predators.

The present behavioral data also demonstrate that JWH and AKB48 qualitatively increase the mouse spontaneous motor activity total distance traveled in a similar way to cocaine 18 — 22 and amphetamine 23 — This behavior, unusual for the mouse, suggests that the administration of SCBs may cause a reduction in the danger perception This finding is in line with previous data demonstrating that CB 1 receptor agonists, at least at low doses, induced anxiolytic effects in rodents 52 , 55 — However, it cannot be ruled out that the motor stimulation effect associated with motor sensory impairment caused by JWH and AKB48 7 , 41 may lead the mouse to a loss of sensory contact with the walls of the box and to the consequent disoriented movements into the open space of the arena.

In fact, spatial information collected by tactile sensations and integrated in visual control in rodents play a pivotal role of spatial orientation 58 , This anxiogenic-like behavior causes greater alertness and attention in the mouse by promoting the combat and flight behavior that is typical of non-predatory animals, such as the mouse This is consistent with the implication of dopaminergic mechanisms in the motor-stimulant properties of amphetamine and cocaine 19 , 62 , In view of this, along with the different behavioral profile of action of the compounds under investigation, in vivo and in vitro experiments have been performed in order to evaluate their effects on dopaminergic system.

In consideration of this finding, in vitro experiments have been performed to verify the possible direct interaction between the two SBCs and DAT.

In fact, previous data proposed that both cannabinoid agonists and antagonists inhibit DAT activity via molecular targets other than CB 1 receptors The present in vitro competition binding experiments clearly indicated that, unlike cocaine and amphetamine, JWH and AKB48 did not bind to DAT expressed in mouse striatal nerve terminals, while they showed only a low affinity micrometer range for human DAT in CHO transfect cell membranes.

The affinity values of cocaine and amphetamine for human DAT, observed in this present study, are in line with literature data 65 , Despite various paper reported the affinity values of GBR , cocaine, and amphetamine in rat striatum, this is the first study, to our knowledge, reporting [ 3 H]-WIN 35, competition binding experiments of these compounds in mouse striatal synaptosomes, where they show affinity values similar to those found on human DAT.

In line with the binding results, this study also demonstrates that, in contrast to cocaine and amphetamine, neither JWH nor AKB48, at the concentration tested, significantly affected [ 3 H]-DA uptake from murine striatal synaptosomes. This is in apparent contrast with some literature data showing that cannabinoids significantly reduces DA uptake in striatal nerve terminals or slices 64 , 67 , However, in line with the present results, a previous study 69 failed to observe alterations of DA uptake following treatment of mouse striatal synaptosomes with some SCBs.

Although other possibility cannot be definitely ruled out, it seems likely that these discrepancies could be due to the different experimental conditions used in the reported studies i. This hypothesis is supported by the present in vivo microdialysis results, showing that the systemic administration of a low dose of JWH 0.

However, in line with the drug behavioral profile, the effect of JWH was long-lasting, while the effect of AKB48 was transient. As expected, either cocaine or amphetamine also increased DA extracellular levels and their effects were significantly higher than those of the two SCBs.

It is well established that the mechanism of action of these classes of drugs is different. Indeed, classical psychostimulants, as cocaine and amphetamine, increase DA neurotransmission by inhibiting the DAT activity in DA nigrostriatal and mesolimbic neuronal terminals; in particular the psychostimulant-induced increase in DA neurotransmission is mainly due to DA reuptake inhibition, an enhancement of DA release or to a combination of the two mechanisms 70 — In fact, while CB 1 receptors are not expressed on midbrain DA neurons 79 , CB 1 receptor activation closely modulates DA neuronal activity, through modulation of local circuitry in the midbrain In mesolimbic DA pathway, CB 1 receptors are located in axon terminals forming either inhibitory or excitatory-type synapses with dopaminergic as well as non-dopaminergic, putative GABAergic, neurons in the VTA, and systemic administration of CB 1 receptor agonists enhances the bursting activity of VTA DA neurons, many of which project to the NAc shell The different mechanisms underlying the SBCs- or psychostimulants-induced DA release are confirmed by the present in vitro studies on striatum, including NAc, nerve ending.

In fact, accordingly to their direct or indirect inhibitory modulation of DAT activity and DA-releasing effects, either amphetamine or cocaine significantly increased [ 3 H]-DA efflux from mouse striatal synaptosomes. In this context, it is worth noting that under the present experimental conditions i. The lack of a presynaptic effect on terminals of nigrostriatal and mesolimbic dopaminergic neurons is also in accord with the absence of CB 1 receptor on dopaminergic terminals see above. Taken together, these findings indicate that, at least at the concentration tested, the two SCBs did not affect the DAT activity, leading to hypothesize that their inhibitory effects on the [ I]-FP-CIT binding to DAT in the mice striatum could be a consequence of an increase in endogenous DA levels.

Create a personalised ads profile. Select personalised ads. Apply market research to generate audience insights. Measure content performance. Develop and improve products. List of Partners vendors. Synthetic cannabinoids, also called synthetic marijuana or fake weed, have been used by many as an alternative to marijuana since products were first introduced in Hundreds of synthetic cannabinoids exist and the effects can be unpredictable and even life-threatening.

Also Known As: There are countless fake weed products being sold as herbal smoking blends, legal bud, herbal smoke, marijuana alternatives, fake weed, or herbal buds. This makes it difficult for parents and other adults to identify them. Drug Class: Synthetic marijuana products are classified as new psychoactive substances NPS , or unregulated mind-altering substances intended to produce the same effects as illegal drugs.

Common Side Effects: Side effects of the drug include elevated mood, relaxation, altered perception, symptoms of psychosis, extreme anxiety, confusion, paranoia, hallucinations, violent behavior, suicidal thoughts, rapid heart rate, raised blood pressure, vomiting, kidney damage, and seizures.

Synthetic marijuana often contains a mixture of dried leaves from traditional herbal plants. They are various colors, including green, brown, blonde, and red, and often sold in small packets approximately two by three inches. The packets are often colorful foil packs or plastic zip bags.

Some online sellers of legal fake weed products do so with disclaimers like "not for human consumption. Fake weed works on the same brain cell receptors as THC or deltatetrahydrocannabinol the psychoactive ingredient in marijuana that gets you high. It is typically smoked, brewed in tea, or vaped. Many of these products are legally marketed as "herbal incense" or "potpourri.

Some people who use herbal buds say that it produces a high similar to that of marijuana, but it doesn't last as long. Others experience a relaxed feeling, rather than the "head high" that real marijuana produces. Also of note is the "harsh" taste, which people say "makes your throat burn and your lungs ache" long after you smoke. Since there are no standards for making, packaging, or selling synthetic weed, it's impossible to know the type and amount of chemicals in each product as well as what the fake weed will do to you.

They have all been found to contain various synthetic cannabinoids, or chemicals produced in laboratories.

Originally, fake marijuana products contained a chemical called HU, which has a molecular structure very similar to THC. Because HU is listed as a Schedule I controlled substance in the United States, these fake weed products were manufactured and sold only in Europe. Since then, new synthetic cannabinoid agonists have been created. They are too numerous to list.

Some are similar in structure to THC; others are not. Some are classified as controlled substances. By using different synthetic marijuana mixtures, manufacturers are able to continue to legally market their products in the United States when another formulation becomes illegal. According to the DEA, the majority of these chemical compounds are produced in Asia with no regulations or standards. Some of these chemicals are still legal. However, since synthetic marijuana first hit the market, more than 20 of these compounds have become controlled in some way at the federal level.

This places them in the same federal category as heroin, crack cocaine, and marijuana. Qualitative methods require less method validation, and the TOF technique acquires data over the whole mass range at all times.

Even though most laboratories do not report positive results unless they have a reference material to compare with, TOF enables the search for emerging substances since the only data required is the accurate mass of the molecule.

There are very few quantitative data for the different synthetic cannabinoids published. These results are in serum and cannot be directly compared with our data in whole blood, as the blood : serum ratios for these substances are unknown. A reasonable extrapolation from THC would propose that the serum concentrations are higher than that in whole blood.

However, this does not seem to be the case in our population of recreational users. In summary, the concentrations are very low and sensitive methods are necessary to both screen and confirm the presence of synthetic cannabinoids in blood.

Despite cannabis being a commonly abused drug, there are few reports of severe intoxications. In comparison with cannabis, the synthetic cannabinoids seem to be more dangerous and potent causing several unwanted symptoms in the users 15 , 38— It is expected that the increased potencies exhibited by many of the cannabinoid agonists will lead to increased adverse effects.

We present eight cases of severe intoxication where synthetic cannabinoids were the only drugs found in the blood of the subjects. Blood samples were taken shortly after apprehension in all cases, and the concentrations were in the higher range among those from our population of recreational users. The subjects also presented with severe symptoms and several were unconscious when found. Somnolence was also one of the most common neurological effects reported by Hermanns-Clausen et al.

Subjects with only JWH present had concentrations between 0. These concentrations, an hour or more after smoking, seem high compared with those obtained as peak within minutes of controlled smoking as reported by Kacinko et al. Therefore, high doses may explain the severe symptoms in our subjects. Compared with cannabis sativa , the dosing of synthetic cannabinoids may be difficult as the application of the active substances on dried plant material may very well not be homogenous within or between batches of products.

Besides the high-affinity and high-efficacy CB1R agonist properties, this may also contribute to the risk of adverse effects. Overdosing might even, under some circumstances, result in death as exemplified by the fatal intoxication described. No other drugs or alcohol were found in the toxicological analyses. We believe that the acute effects of the synthetic cannabinoids played a significant role in the demise of this young man.

Tandem mass spectrometry is a requirement and the diversity of analytes makes it difficult to use only one extraction and detection method to cover the whole range of cannabinoids in a quantitative method.

For the toxicology laboratory, target methods quickly become less useful when the drug panorama changes. For the future, a more general untargeted method might be a better approach to counter the continuous change in substances. We are now investigating the use of LC—QTOF for the untargeted screening of synthetic cannabinoids in blood and urine.

The toxicity of the synthetic cannabinoids seems to be worse than that of natural cannabis probably owing to the higher potency and perhaps also to the presence of several different cannabinoids in the smoked incense and the difficulties of proper dosing.

The acute toxic effects may, under certain circumstances, contribute to death. Google Scholar. Oxford University Press is a department of the University of Oxford.

It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide. Sign In or Create an Account. Sign In. Advanced Search. Search Menu. Article Navigation.

Close mobile search navigation Article Navigation. Volume Article Contents Abstract. E-mail: robert. Oxford Academic. Markus Roman. Mikael Andersson. Arne Eklund. Select Format Select format. Permissions Icon Permissions. Abstract In recent years, several synthetic cannabinoid compounds have become popular recreational drugs of abuse because of their psychoactive properties.

Table I List of synthetic cannabinoids scheduled in Sweden. Scheduled as. Date of ban. Open in new tab. Table II MS method parameters. Mass parameters. Retention time min. Tobacco is one option but this risks nicotine addiction Limit use by using occasionally, such as monthly or during holidays so that your mind and body have time to recover.

When to get help If someone falls unconscious after smoking synthetic cannabinoids they could die. Ask loudly if they are OK. Shake them gently If they are not responsive, dial and request an ambulance Check they are breathing and place them in a stable side position. If they are not breathing start chest compressions. Always call an ambulance if someone: is unconscious stops breathing has a seizure is extremely agitated for longer than 15 minutes has chest pain or breathing difficulties for longer than 5 minutes.

Things to look out for Synthetic cannabinoids are very addictive They can make you anxious and can make mental health problems worse Each batch can vary greatly An unpleasant comedown can come on fast and make you want to take more.

Seek help to manage more serious withdrawal symptoms such as: difficulty stopping use weight loss suicidal feelings paranoia, anxiety and panic attacks uncontrollable anger. Cutting down or stopping use Cutting down or stopping use You could have a substance use disorder if you are: using synthetic cannabinoids more than you want to finding it hard to stop missing school, work or family commitments always thinking about synthetic cannabinoids need to use a lot to get the same effect.

Drug Index We believe that access to accurate, clear information is essential to reduce drug-related harm.