About

Providing straightforward information pertaining to drugs, drug use & drug policy. The Grey Pages promotes drug-related literacy and advocates a system of viable and tolerant drug policies. This is my personal collection of commentaries, essays, tid-bits, and other such writings on everything ranging from drug use, drug policy and drug-myths, to drug-science, addiction, human behavior, and the workings of the human brain. I started this blog with a particular focus on opioids, and over the past year have found my interest gravitate toward the intriguing, ever-changing world of designer intoxicants (i.e. "research chemicals" or "designer drugs").

Wednesday, March 20, 2013

Rolling, Rolling, Rolling - Stimulating Empathogens of the MDMA Type

Methylone:

Basic:

Source: Erowid.org
Other common names include bk-MDMA, M1, or MDMC. Methylone is a substituted cathinone with empathogen and stimulant properties. It may be considered an analogue of MDMA as well as methcathinone.

This drug is very similar to MDMA, not only chemically, but in its mode of action as well as well. Methylone had originally been researched and patented as an antidepressant in the 1990's, but was never marketed commercially.

Chemistry:

Put simply, methylone is the beta-ketone analog of MDMA (ecstasy). It is related to methcathinone in the same way MDMA is related to methamphetamine. It is best described as an analog of MDMA where the beta carbon contains a ketone group.

Mode of Action:

Methylone is believed to induce the release of the monoamine neurotransmitters while inhibiting their reuptake as well; leading to increased flow of monoamine transmission throughout the brain and CNS. Its affinity for the serotonin transporter is somewhat lesser than that of MDMA, while its affinity for dopamine and norepinephrine transporters is comparable to MDMA. 

Effects:

Based on its pharmacological profile, methylone is likely to produce moderate empathogenic effects, with strong euphoric-stimulant effects similar to MDMA.

Butylone

Basic:

Butylone is a compound of the substituted cathinone family and is also known as bk-MBDB. It produces stimulant and mild enactogen effects and has been sold as a research chemical. 

Chemistry:

Butylone is the chain lengthened homologue of methylone (bk-MDMA). It differs from methylone in that it contains an ethyl rather than a methyl group at the alpha carbon. Butylone is also the beta-keto homologue of MBDB.

Mode of Action:

Butylone produces stimulating enactogenic effects. Its mode of action involves potentiation of monoamine pathways, presumably through inhibition of serotonin, norepinephrine, and dopamine reuptake transporters and possibly through increased monoamine release.

Effects:

Users have reported predominantly stimulant reactions, though its effects have also been compared to methylone (though higher relative doses are required), as well as MDMA. Positive results have been reported with a combination of butylone and methylone. Jaw tension or grinding similar to that caused by ecstasy has been reported. There are limited reports of mild empathogenic effects. Users report an enhanced enjoyment of music and tactile sensitivity.

Side effects may include gastric distress, "tweakiness", muscle tension, and anxiety or dysphoria, all of which have been reported by some users.

Typical dosages seem to range from 25-75mg, though some have reported oral dosages of 100mg or more, while effects generally last 2-3 hours, depending largely on dose and route of administration.

Pentylone (bk-MBDP)

Basic:

Pentylone is a centrally acting compound of the substituted cathinone family with psychostimulant and euphorigenic properties. It was originally synthesized in the 1960's and is/has been marketed as a research chemical and designer drug. Pentylone was present in the original ivory wave novelty product in a 1:1 ratio with MDPV.

Chemistry:

Pentylone is the 3,4-methylenedioxy analogue of pentedrone, and can be considered the methylamino analogue of MDPV.

Mode of Action:

Pentylone is believed to act as a releasing agent and/or reuptake inhibitor of dopamine, norepinephrine, and possibly serotonin.

Effects:

The effects of pentylone are comparable to those of other 3,4 methylenedioxy-cathinone-type stimulants (i.e. stimulating and enactogenic), and last 2 to 3 hours. It can be taken by oral, intravenous, intranasal, and rectal routes. It may also be vaporized and inhaled. Users who smoke pentylone report a greater level of "tweakiness". Its effects have been compared to those of cocaine by intranasal or vaporized routes.


Reported dosages range from as low as 10mg to as high as 100mg or more; route of administration is a major factor. It can be swallowed, snorted, injected or vaporized ("smoked"). Swallowing pentylone requires significantly higher dosages.

Ethylone (MDEC, bk-MDEA) 

Basic:

Ethylone is a cathinone-based compound with stimulant, enactogen, and psychedelic properties. It is a relative of methylone and has been sold as a research chemical/designer drug. Ethylone has a very short history of human use and little is known regarding its toxicity or safety profile. 

Chemistry:

Ethylone is the cathinone equivalent to MDEA ("Eve"), and differs only in containing a ketone at the bata side chain position. 

Mode of Action:

The pharmacological profile of this compound has not been studied, though it is likely to produce its effects via potentiation of monoamine + serotonin pathways.

Effects:

Ethylone can be expected to produce effects similar to butylone or other methylenedioxy-cathinones, with typical doses seeming to range from 50-150mg based on user reports. 

According to some users, ethylone may very well be described as a less potent alternative to methylone. Ethylone is sometimes taken alongside methylone or butylone for an enhanced set of effects.

This was taken as an excerpt from my entry on Substituted Cathinones

Thursday, March 14, 2013

Hawaiian Baby Woodrose (Seeds)

Hawaiian Baby Woodrose, or HBW,  is a climbing vine known by the botanical name Argyreia Nervosa. It is encountered in the Carribean, Africa, and areas of Hawaii. It bears small seeds which look very much like small chocolate chips. The seeds are often collected and consumed for the psychedelic alkaloids they contain. 

HBW seeds contain ergine, known also as lysergic acid amide or LSA, an ergoline derivative closely related to LSD.

Currently, HBW is not a controlled substance in the US, however the LSA they contain is listed as a schedule III controlled substance.

User reports on HBW seeds suggest that not many seeds are required for an effect. Psychedelic effects become apparent with 4 or more seeds eaten on an empty stomach.

LSA is believed to act similarly to most classical hallucinogens; It is likely to exhibit agonist and/or partial agonist activity at multiple serotonin receptors, including the 5HT-2A subtype.

The effects of LSA are similar to the effects of LSD, and are reported to be less intense. The experience typically lasts 6 to 8 hours, though a pleasant afterglow may linger for up to 12 hours.

Psychological effects of LSA include Introspection, Altered cognitive process, Laughing or an urge to laugh, Closed or open eye visual distortions such as spots, light tracers, color shifting, distortion of surface textures, brightened or enhanced colors, Enhancement of sensory input such as taste, smell, sound, or vision, and Time distortion. Physiological effects include Dilated pupils (mydriasis), Increased heart rate, CNS stimulation or sedation, Insomnia, Stomach pain or cramps, and Mild to severe nausea and vomiting (some reccommend taking a regular dose of dimenhydrinate or diphenhydramine 30 minutes before consuming the seeds).

Likely After-Effects include Possible "hangover" characterized by blurred vision with vertigo or dizziness, and an ability to acheive a deep or refreshing sleep following the experience.

Sunday, March 10, 2013

ACLU Makes Biggest Effort Yet to Assess Growth of America's Police State

The American Civil Liberties Union has filed 255 public records requests in 23 states, as well as with the Army National Gaurd, in order to examine the increasing militarization of state, county, and local police departments. Read more here and here.

Sunday, March 3, 2013

Biological Actions of Various Pyrovalerone-Family Compounds on Monoamine Systems

Very Potent NDRI's Indeed:

Ki Values indicate binding affinity

IC50 values indicate level of intrinsic activity (measured by the amount of a given compound it takes to inhibit the function of a monoamine transporter by 50%)

DAT/DA = Dopamine 
NET/NE = Norepinephrine
SERT/SER = Serotonin

Cocaine (Reference Standard)
DAT Ki: 432 ± 29
DA IC50: 461 ± 46

NET Ki: 2150 ± 190
NE IC50: 378 ± 48

SERT Ki: 358 ± 24
SER IC50: 494 ± 51

APVP
DAT Ki: 33.7 ± 5.4
DA IC50: 52.3 ± 6.2

NET Ki: 199 ± 45
NE IC50: 56.0 ± 13

SERT Ki: >10┬ÁM
SER IC50: ???

Pyrovalerone (Racemic)
DAT Ki: 21.4 ± 4.6
DA IC50: 52.0 ± 20

NET Ki: 195 ± 26
NE IC50: 28.3 ± 8.1

SERT Ki: 3770 ± 560
SER IC50: 2780 ± 590

S-Pyrovalerone 
DAT Ki: 18.1 ± 3.0
DA IC50: 16.3 ± 2.3

NET Ki: 109 ± 45
NE IC50: 11.3 ± 2.4

SERT Ki: 2220 ± 550
SER IC50: 1070 ± 230

Naphyrone
DAT Ki: 20.1 ± 7.1
DA IC50: 40.0 ± 13

SERT Ki: 33.1 ± 1.1
SER IC50: 46.0 ± 5.5

NET Ki: 136 ± 27
NE IC50: 11.7 ± 0.9

3,4-Dichloropyrovalerone 
DAT Ki: 11.5 ± 1.4
DA IC50: 43.0 ± 20

SERT Ki: 199 ± 50
SER IC50: 600 ± 63

NET Ki: 37.8 ± 3.2
NE IC50: 21.0 ± 0.6


Meltzer PC, Butler D, Deschamps JR, Madras BK. 1-(4-Methylphenyl)-2-pyrrolidin-1-yl-pentan-1-one (Pyrovalerone) analogues: a promising class of monoamine uptake inhibitors. Journal of Medicinal Chemistry. 2006 Feb 23;49(4):1420-32.

PMID: 16480278
DOI: 10. 1021/jm050797a


Saturday, March 2, 2013

Generic Suboxone? What happened?

For roughly 4 years we've awaited a generic version of Suboxone to become available. 

However, by the time the patent expired on the original Suboxone tablets, Reckitt Benckiser (its manufacturer) had aquired an exclusive new patent, on an exclusive, new form of their product. Their new product was Suboxone film; the same medication, only rather than in tablet form, it came in the form of paper-thin film strips, each enclosed in a plastic wrapper.

Around the same time, in order to avoid generic competitors from introducing a cheaper suboxone tablet to the market, RB took some bold measures; first, they convinced private insurers that their former tablet formulation of Suboxone was unsafe, and emphasized the possibility of the tablet being consumed by young children. 

They introduced the "new and improved" formulation; film strips, each individually wrapped in a child-proof container. RB convinced many insurers that they should no longer provide coverage for the tablet formulation (or at least not without the doctor justifying, in writing, why the tablet form was nessessarry), and that they should exclusively cover the new, patent-protected film formulation, which only their company could produce.

Insurance providers bought it. Subsequently, the manufacture and marketing of a generic suboxone became unappealling, due to the limited profits it would produce (remember, RB convinced many insurers to only cover the new version of the drug). This bought some time, and further delayed the possibility of a generic being introduced to the market. 

Roughly 3 years later, RB sent a CITIZENS PETITION to the FDA claiming that its original product (the tablets) was a "bad drug", and requesting that a ban be placed on its manufacture and sale, in order to "protect the public" from their previous tablet formulation. 

Had the FDA granted this request, all generic manufacturers would have been prevented from ever introducing a generic suboxone tablet (a prospect which, until that point, would have been inevitable). RB would have been left to dominate the market, with an overpriced and overhyped, patent protected, suboxone film.

However, in recent days, the FDA denied Reckitt's petition. Long story short; the door remains open for a generic product to be made available. When or if this will happen is another question - though it's quite likely  to happen in the near future, as RB has as of mid-march discontinued the tablet formulation of suboxone. In the meantime, the film is available in two new dosages; one containing 4 mg buprenorphine, and another containing 12 mg buprenorphine.

Read more here


Piperazines

BZP

Known chemically as benzylpiperazine. BZP is a psychostimulant compound and a derivative of piperazine. 

Its use was documented in clinical literature as early as the 1950's; more recently it has appeared as a research chemical and recreational drug. It became a popular grey market/"legal high" product in the US and elsewhere in the early 2000's but has since been listed as a schedule 1 controlled substance in the US. Its effects are similar to amphetamine or methamphetamine.

BZP acts as a mild to moderate releaser of dopamine and norepinephrine, and a weak serotonin releaser. It is also thought to inhibit the reuptake of serotonin, norepinephrine, and dopamine. 

The oral route has been common for BZP users, with dosages up to 150 mg. Its effects last several hours.

Adverse effects have included kidney damage and seizures.

TFMPP

Chemically known as trifluoromethylphenylpiperazine. TFMPP is a piperazine derivative and an analogue of BZP. It has been marketed as an MDMA alternative. It was temporarily listed as a controlled substance in the US through the DEA's emergency scheduling procedure, but the ban was allowed to expire without renewal.

It differs pharmacologically from benzylpiperazine in that it produces enactogen effects rather than stimulant-enactogen effects. Its monoaminergic action is almost exclusively serotonergic. TFMPP binds to multiple 5HT receptor subtypes as a full agonist, and shows partial agonist efficacy at the well known 5HT2A subtype. It is also a serotonin reuptake inhibitor/releasing agent, with little to no effect on dopamine or noradrenaline.