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Buy jwh 018 spray online is an aminoalkylindole used as an active ingredient of products sold as cannabis substitutes. When smoked, JWH-018 produces cannabimimetic effects in doses lower than the doses of Δ9-tetrahydrocannabinol (THC) needed to produce effects of similar strength (higher potency). Many of the risks linked to cannabis use are also present in the case of JWH-018, among them complications in patients suffering from cardiovascular diseases and triggering of acute psychosis. Abuse potential and dependence potential seem to be similar to cannabis. One of the major differences between cannabis and this synthetic cannabinoid is the greater acute toxicity of JWH-018. Due to its full agonistic action at the CB1 receptor, the side effects of higher doses can be life-threatening. This is aggravated by the fact that dosing is very difficult due to changing contents of active ingredients in different products, different batches of the same product and even within one packet. Regarding chronic toxicity, risks are very difficult to estimate on the basis of the available data. However, there are concerns about potential carcinogenic effects. jwh 018 spray for sale legit.

Physical properties
White crystalline solid (in pure form)

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A. International Nonproprietary Name (INN) Not applicable

Chemical Abstract Service (CAS) Registry Number 209414-07-3

Other Names JWH-018, AM-678

Street Names ‘Spice’, ‘K2’, ‘legal weed’, ‘synthetic cannabis’, ‘herbal incense’

JWH-018 was found as an additive in more than 60 different brands of ‘herbal mixtures’ in Germany alone (own unpublished data). These products were carrying fantasy names like e.g.: ‘Atomic Bomb’, ‘Dragon’, ‘Monkees Go Bananas’, ‘Rockstar’, ‘Spike 99’, ‘Ultra’ and ‘Wasted’.

Mixtures sold under specific brand names do not always contain the same substance or mixture of substances over time.

Physical properties

White crystalline solid (in pure form)

WHO Review History

JWH-018 was not previously pre-reviewed or critically reviewed. A direct critical review is proposed based on information brought to WHO’s attention that JWH-018 is clandestinely manufactured, of especially serious risk to public health and society, and of no recognized therapeutic use by any party. Preliminary data collected from literature and different countries indicated that this substance may cause substantial harm and that it has no medical use.

Chemistry

Chemical Name

IUPAC Name: Naphthalene-1-yl(1-pentyl-1H-indol-3-yl)methanone

CA Index Name: 1-Naphthalenyl(1-pentyl-1H-indol-3-yl)-methanone

Chemical Structure

Molecular Formula: C24H23NO Molecular

Weight: 341.45 g/mol

Melting point: 65-67°C [27] or 51,9°C [97] Boiling point: N/A Fusion point: N/A

Synthesis

Synthesis of JWH-018 can be carried out in analogy to the synthesis strategies described for various aminalkylindoles [12, 27, 49]. 1H-indol-3-yl(naphthalen1-yl)methanone is prepared by Friedel-Crafts acylation using 1-H-indole and naphthalene-1-carbonyl chloride (prepared from naphthalene-1-carboxylic acid and thionyl chloride). Afterwards, N-alkylation is performed by addition of 1- bromopentane. The synthesis can also be performed vice versa. Common precursors are the above mentioned 1-H-indol, naphthalene-1-carbonyl chloride and 1-bromopentane. Alternatively, 1-pentyl-indole can be used as a precursor in order to skip the N-alkylation step. products that contain jwh-018

Commercially available domestic or industrial products, which could be used for synthesis may contain other potentially toxic substances, including heavy metals and organic solvents. Use of such products as reagents may result in serious toxic effects if the resultant impure product is consumed. The herbal material which is used as a basis for the smoking mixtures may contain toxicologically relevant substances like e.g. pesticides, too. products that contain jwh 018

Chemical description

JWH-018  is a naphthoylindole alkylated at the indole nitrogen.

Chemical properties

Chemically, JWH-018 can be regarded as relatively inert as it is substituted at the reactive C-3 position with the naphthoyl moiety. Due to the aromaticity of the indole system the nitrogen does not lead to considerable basicity.how to make jwh 018 spray

Chemical identification

The analytical profile of JWH-018 has been described in various papers. Utilized methods include LC-MS/MS[90], GC-EI-MS [23, 28, 33, 67, 101, 103, 105, 118, 119], HRMS [39, 48, 89], NMR [66, 101], IR-ATR [97], and UV-VIS detection [37, 101, 103]. Detection in biological matrices was described in serum [30, 58, 75, 98] [31], whole blood [6, 45, 55, 63, 91, 100, 115], hair [51, 57, 84], and oral fluid [25, 59, 60, 82, 96] targeting JWH-018. In urine samples, the main metabolites are the analytical targets [7, 20, 26, 40, 50, 71, 113]. buy jwh 018 powder online without prescription

Ease of convertibility into controlled substances

JWH-018 is not considered an immediate precursor of any internationally controlled substance [5].

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Pharmacodynamics

JWH-018 possesses a relatively high binding affinity (expressed as IC50 (occupation of 50% of the receptors)) towards the cannabinoid receptor type 1 (CB1) of 9.0 nM ± 5 and towards the cannabinoid receptor type 2 (CB2) of 2.94 nM ± 2.65 [9, 111, 112] compared to the binding affinities of delta-9 tetrahydrocannabinol (THC) of 40.7 nM ± 1.7 at the CB1 and 36.4 nM ± 10 at the CB2 receptor [24, 92]. Chimalakonda et al. tested the biological effects by applying an in vitro [35S] guanosine-5’-O-(3-thio)- triphosphate ([35S]GTPγS) binding assay and the compound showed full agonistic properties [21]. JWH-018 induces inhibition of forskolin-stimulated cAMP accumulation in CHO cell lines expressing CB1 receptors with an EC50 14.7 ± 3.9, maximum inhibition 79% [22] and in Neuro2AWT cells with an EC50 of 5.31 ± 0.4 nM [17]. Based on this data and clinical observations, it can be assumed that JWH-018 shows typical effects of CB1 agonists including sedation, cognitive dysfunction, tachycardia, postural hypotension, dry mouth, ataxia, immunosuppression and psychotropic effects. purchase jwh-018 powder

A pronounced difference with regard to THC is the formation of potential pharmacologically active JWH-018 metabolites. While in the case of THC, only one of the major THC-metabolites is known to be psychoactive and retains binding affinity towards cannabinoid receptors (11-OH-THC: Ki at the CB1 receptor: 38.4 nM ± 0.8 [24]), several JWH-018 metabolites retain high CB1 receptor binding affinity (relative rank of binding affinities: JWH-018 > JWH-018 N-(4-OH-pentyl) > JWH-018 N-(5- OH-pentyl) > JWH-018 (5-OH-indole) = THC = JWH-018 (6-OH-indole) = JWH-018 N-(5-OH-pentyl) > JWH-073 N-(4-OH-butyl)) >> JWH-018 pentanoic acid [15, 16, 21]). Furthermore, full agonistic binding has been shown for JWH-018, JWH-018 (5- OH-indole), JWH-018 (6-OH-indole) as well as for JWH-018 N-(5-OH-pentyl). jwh 018 for sale at huge discount

applying [35S]GTPγS binding assays, and partial agonist activity for JWH-073 (6-OHindole) and JWH-073 N-(4-OH-butyl) [15, 16, 21]. The glucuronidated JWH-018 N-(5- OH-pentyl) metabolite retains binding affinity towards the CB1 receptor and activity as a neutral antagonist (Ki: 922 nM) [88]. No data is available concerning the question whether this metabolite of JWH-018 is capable of antagonizing pharmacological effects of JWH-018 in vivo, and if sufficient concentrations are formed at the site of action. jwh 018 spray for sale

Similar to the retention of CB1 receptor affinity, metabolites of JWH-018 also bind with high affinity at the CB2 receptor (relative rank of binding affinity: JWH-018 > JWH073 > THC > JWH-073-N-(3-OH-butyl) > JWH-018 N-(5-OH-pentyl) > JWH-018 (6- OH-indole) > JWH-018 N-(4-OH-pentyl) > JWH-073 N-(4-OH-butyl) > JWH-073 (6- OH indole) >> JWH 018 pentanoic acid and JWH-073 butanoic acid). Utilizing a [35S]GTPγS binding assay and an adenylyl cyclase assay to measure intrinsic activity, JWH-018 showed full agonist activity at CB2 receptors. The results from measuring the binding affinity as well as the intrinsic activity suggest that JWH-018 binds more efficiently to CB2 receptors thus requiring occupancy of fewer receptors to produce equivalent levels of adenylyl activity [81]. As CB2 receptors are predominantly expressed in various immune cell types, JWH-018 uptake might modulate immune function which could lead to immune suppression. jwh 018 spray bottle

Investigations on effects of JWH-018 on 12-O-tetradecanoylphorbol-13-acetate (TPA) induced inflammation and carcinogenesis in mice were carried out by Nakajima et al., showing a higher anti-inflammatory activity of JWH-018 when compared to indomethacin [74]. Furthermore, JWH 018 (0.02 µM JWH-018/mouse and 0.2 µM JWH-018/mouse) inhibited tumor promotion by TPA in mouse skin carcinogenesis model.

Neuropharmacology and effects on the central nervous system Atwood et al. investigated the effects of JWH-018 on glutamatergic neurotransmission in cultured autaptic hippocampal neurons and activation of ERK1/2 mitogen activated protein kinase (MAPK) as well as the internalization of CB1 receptors [8]. JWH 018 inhibited excitatory postsynaptic currents in a concentration and CB1 receptor dependent manner (IC50: 14.9 nM), increased MAPK phosphorylation and induced rapid and robust receptor internalization, therefore indicating that the typical effects after JWH 018 consumption are very likely due to CB1 receptor activation. buy jwh 018

A case report published by Rominger et al. describes short-term alterations of dopamine D2/3 receptors availability in a patient before and after acute detoxification from a ‘herbal mixture’ product, concluding that consumption of synthetic cannabinoids can lead to serious health problems, where substantial alterations of the dopaminergic system have to be taken into account [83]. Unfortunately, the consumed herbal mixture was not analyzed in this case and as a consequence no conclusion can be drawn on which synthetic cannabinoid was consumed.

Effects on cardiovascular, respiratory, gastrointestinal, liver, kidneys and genitourinary systems No study data available. However, a marked elevation of the heart rate is one of the clinical signs very often seen after intoxication with synthetic cannabinoids.

Behavioural studies in animals

Behavioural effects in mice after the inhalation of smoke from 200 mg of a herbal mixture containing 3.6% JWH-018, 5.7% JWH-073 and less than 0.1 % JWH-398 were studied utilizing the tetrad test (response in all four categories suggest CB1 activity) by Poklis et al. [79]. After inhalation the body temperature of all tested mice dropped more than after smoking of 200 mg marijuana (3.5 % THC), and the mice remained cataleptic for at least 20 min. Wiebelhaus et al. also performed tetrad testing in mice, by exposing the animals to the smoke of 10, 20 or 50 mg of a 5.4% JWH-018 containing herbal mixture [109]. The study animals showed hypomotility, antinociception, catalepsy, and hypothermia in a dose related manner. The behavioural effects were blocked by rimonabant (CB1 receptor antagonist), strengthening the observation that the effects are mediated by CB1 receptor activation. Further observations in the study animals included ptosis, hyperreflexive responses and straub tail. 50 mg of the herbal mixture was found to produce similar effects as 200 mg marijuana (14.8 mg THC). In both studies JWH018 was detected in the brain tissue of the animals. Wiley et al. also observed hypomotility, antinociception, catalepsy, and hypothermia in mice after injection of JWH 018. where to buy jwh 018 in stores

Based on drug discrimination studies carried out in THC trained rats, JWH 018 appeared to be 8 times more potent than THC. Presence of rimonabant resulted in a 4.4- fold parallel shift to the right of the JWH-018 dose-response curve, suggesting antagonism and mediation through CB1 receptors [53, 54]. Additionally, drug discrimination studies were also carried out in THC trained rhesus monkeys by Ginsburg et al. [38]. In the tested monkeys JWH 018 also increased the response on the THC-lever in a dose dependent manner and was 3.4-fold more potent than THC. However, THC had a significantly longer duration of action compared with JWH 018 (4 h vs. 2 h). The same authors also carried out drug discrimination studies in rimonabant trained rhesus monkeys, whereas JWH 018 dose-dependently decreased the response rate, indicating a mediation of the THC-like effects through CB1 receptors. This is in accordance to the results obtained from the drug discrimination studies in rats. jwh 018 alternative

As a consequence from the above drug discrimination study data, it can be concluded that JWH 018 is pharmacologically active and users are likely to experience marijuanalike effects. Furthermore, Ginsburg et al. come to the conclusion that the shorter duration of action could evoke a more frequent use, and might therefore increase abuse and dependence liability [38]. jwh 018 supplier

Investigations of the effects of JWH-018 on electroencephalogram (EEG) power spectra and locomotor activity in rats by Uchiyama et al. indicated that the effect on the EEG is different from that of THC as JWH-018 increased the EEG power up to 3.9 fold and reduced the EEG activity, whereas THC reduced the EEG power [102]. Furthermore, locomotor activity was reduced more strongly and for a longer time by JWH 018 than by THC. The experiments showed that JWH 018 changed the EEG power spectra and suppressed the locomotor activity of rats more significantly and for a longer duration than THC, indicating potent pharmacological action in the central nervous system. how to make jwh 018

Vardakou et al. reported the observation of a severe lethargic, unresponsive catatonic state at all doses tested in a rat repeat dose study (0.1 to 10 mg/kg). Furthermore, at 10 mg/kg breathing frequency decreased and one rat died. However, the exact methodology of the study is not stated [107]. buy jwh 018 liquid

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