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Buy JWH-147 JWH-147 JWH-030 JWH-030. JWH-147 for sale is an analgesic drug used in scientific research, which acts as a cannabinoid agonist at both the CB1 and CB2 receptors. It is somewhat selective for the CB2 subtype, with a Ki of 11.0 nM at CB1 vs 7.1 nM at CB2. It was discovered and named after John W. Huffman.

Legal status JWH-147 JWH-147 JWH-030 JWH-030

In the United States, CB1 receptor agonists of the 3-(1-naphthoyl) pyrrole class such as JWH-147 are Schedule I Controlled Substances.

JWH-147 was banned in Sweden on 1 October 2010 as harmful to health, after being identified as an ingredient in “herbal” synthetic cannabis products.

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Buy JWH-147 JWH-147 JWH-030 JWH-030. Marijuana (Cannabis spp.) is usually marketed as dried leaves and buds. These plant parts are rich in chemicals, with over 60 compounds which are unique to this genus and thus are called ‘cannabinoids’ (CB). Many, including cannabidiol and cannabigerol, have diverse, pronounced physiological effects in mammalian systems.^1,2 One CB in particular, Δ⁹-tetrahydrocannabinol (THC), has drawn interest because of its psychoactive and analgesic effects. The remarkable mixture of CBs and other phytochemicals in marijuana has driven its use throughout the world for medical, recreational, and spiritual purposes for five millennia. Buy JWH-147 JWH-147 JWH-030 JWH-030

The Pursuit of Synthetic CBs

Legal, commercial, and medical issues support the development of synthetic CBs. In the United States, the FDA, which supervises the approval of new drugs, must evaluate each active compound with its associated inactive ingredients, which may, for example, affect pharmacokinetics. As may be expected, different varieties of Cannabis have unique ratios of CBs and other chemicals, and, like distinct formulations of prescription drugs, have discrete physiological effects. Marijuana simply cannot be evaluated as a drug by the FDA. Botanical preparations may, in FDA parlance, be called ‘dietary supplements’ and may claim to offer health benefits, but they must also explicitly disclaim ability to treat or prevent disease.

While inhaling the smoke of marijuana has negative respiratory effects and many purported benefits of cannabis are anecdotal or less effective than existing therapies,⁴ it is clear that marijuana and THC analogs affect pain, nausea, appetite, immunity, memory, and mood. Although medications or treatments exist for each of these conditions, there is significant room for improvement, and each represents a huge commercial market. The challenge is developing an FDA-approvable formulation using an active compound or compounds from marijuana, or their analogs. The search skyrocketed after the elucidation of the molecular structure and actions of THC.

The primary receptors targeted by THC are G_i protein-coupled receptors known as CB₁ and CB₂. As with other G_i-linked receptors, the activation of CB₁ or CB₂ typically blocks the activation of adenylate cyclase, preventing signaling through cyclic AMP. Significantly, CB₁ or CB₂ differ in their distribution, so they subserve distinct roles. CB₁ is predominantly localized in the central nervous system (CNS) and has critical actions in suppressing neuronal signaling, particularly that related to mood, stress, appetite, and memory.⁵ The receptor was the first one described to be involved in retrograde neuronal signaling: it is localized, within neuronal junctions, on the presynapse. Its activation can produce a reduction in the release of neurotransmitters. Normally, signaling through the synapse by neurotransmitters can result in the synthesis of natural endocannabinoids, with their subsequent secretion into the synapse, leading to retrograde signaling back to terminate neurotransmitter release. CB₂, on the other hand, is primarily found on immune cells, both throughout the peripheral vascular system and in the CNS. Activation of this G_i-linked receptor profoundly suppresses immune cell function and pain.⁵ It is important to note that, beyond these generalizations, there is some overlap in the distributions and actions of the two receptors. CB₁ can be found peripherally and CB₂ has neuronal sites, and both are involved in nociception.Buy JWH-147 JWH-147 JWH-030 JWH-030

Synthetic THC Analogs and Synthetic Cannabinoids

The first THC analogs, including HU-210 and CP-47,497 (Figure 1), were developed in the 1980s. Their introduction allowed, first, the localization and types of responses evoked by THC analogs, and, subsequently in the early 1990s, the discovery of CB₁ and CB₂. Cannabimimetic actions of CP-47,497 included analgesic, motor depressant, anticonvulsant, and hypothermic effects, as well as increased vocalization in dogs.⁶ An independent search for novel antinociceptive compounds, based on known NSAIDs, introduced the structurally distinct (aminoalkyl)indoles, like WIN 55,212-2.⁷ Surprisingly, WIN 55,212-2 binds both CB₁ and CB₂ (K_i = 1.⁹, 0.28 nM, respectively) with higher affinities than does THC (K_i = 41 and 36 nM, respectively). This breakthrough molecule led John W. Huffman, working at Clemson University, to conclude after some simple modeling that “a simple alkyl chain could replace the aminoalkyl group” (personal communication). The investigation of hundreds of related “JWH compounds”, characterized primarily by their binding affinities for CB receptors, ensued. Buy JWH-147 JWH-147 JWH-030 JWH-030

Figure 1. THC, THC analogs, and cannabimimetic

JWH 018 is the prototypical JWH compound (Figure 2). Its high potency (CB₁ K_i = 9.0 nM, CB₂ K_i = 2.94 nM) and non-THC structure made is a desirable component of many Spice/K2-type herbal blends.^8,9 Typically, a specific herbal sample, commonly promoted as ‘incense’ and ‘not for human consumption’, contained multiple synthetic CBs (e.g., JWH 018, JWH 073, or a C8 homolog of CP 47,497), natural endocannabinoids (e.g., oleamide), as well as other substances (e.g., eucalyptol, α-tocopherol).^8,10,11 In an effort to develop generic legislation to control all synthetic CBs, the Advisory Council on the Misuse of Drugs (ACMD; United Kingdom) developed a structural classification of JWH compounds.¹² The Group 1 naphthoylindoles is typified by JWH 018 and includes 73 other compounds. The related Group 2 naphthylmethylindoles contains 9 compounds (e.g., JWH 175 (CB₁ K_i = 22 nM)).¹³ Several of the 32 known naphthoylpyrroles (Group 3) are potent CB receptor agonists (JWH 147: CB₁ K_i = 11 nM, CB₂ K_i = 7.1 nM)¹⁴ and therefore have a high abuse potential. The Group 4 napthylmethylindenes has 3 members, like JWH 176 (CB₁ K_i = 26 nM).¹³ Finally, the Group 5 phenylacetylindoles covers 28 synthetic CBs, like JWH 203 (CB₁ K_i = 8 nM, CB₂ K_i = 7 nM)¹⁵, some of which have been detected in blends.^{16-19 Buy JWH-147 JWH-147 JWH-030 JWH-030}

Figure 2. Examples of four major classes of JWH compounds

THC analogs, like HU-210 and CP 47,497, and certain first-generation synthetic CBs, like JWH 018 and JWH 073, have largely been regulated worldwide. They have been replaced by similarly potent JWH compounds, including naphthoylindoles (e.g., JWH 081, JWH 122, JWH 200, JWH 210, JWH 398) and phenylacetylindoles (e.g., JWH 203, JWH 250, JWH 251).^16,20,21 In addition, AM2201 (Figure 3), an “AM-type” compounds described in a patent by Alexandros Makriyannis, has emerged.²² This patent also introduced benzoylindoles, like AM679. Also common is UR-144, developed by scientists at Abbott, who included a tetramethylcyclopropyl group to confer selectivity for the CB₂ receptor.²³ While selective for CB₂, this compound still binds CB₁ effectively (K_i = 150 nM), presumably explaining its popularity. Both the Makriyannis patent and the Abbott report describe dozens of additional compounds which are candidates for abuse. Buy JWH-147 JWH-147 JWH-030 JWH-030

Figure 3. Structures of some non JWH-type synthetic CBs

Several additional synthetic CBs are structurally distinctive. The replacement of the indole core of the JWH CBs with a benzimidazole core, as in AZ-11713908 (Figure 3), gives significant CB₂ selectivity.^24,25 A series of compounds using a quinolone core also have high affinities for CB receptors, as well as effectiveness in vivo.^26,27 The addition of an adamantylamino group to a quinolone base, as in SER-601, confers selectivity for CB₂ over CB₁ (CB₁ K_i = 6.3 nM, CB₂ K_i = 1220 nM).²⁷ The adamantylamino group also appears on newer synthetic CBs, replacing the naphtyl groups of JWH 018 and AM2201 to generate 2NE1 and STS-135, respectively. The combination of a tetramethylcyclopropyl group and a thiazolylidene base gives A836,339, which, although CB₂-selective (CB₁ K_i = 270 nM, CB₂ K_i = 0.64 nM), activates CNS CB₁in vivo at higher doses.²⁸ The combination of neuronal pain suppression via CB₂ with milder psychoactive effects through CB₁ distinguishes A836,339 from the synthetic cannabinoids with higher affinities for CB₁. Buy JWH-147 JWH-147 JWH-030 JWH-030