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#127 METHYL-DOB

4-BROMO-2,5-DIMETHOXY-N-METHYLAMPHETAMINE


SYNTHESIS: To a solution of 6.0 g of the free base of 2,5-dimethoxy-N-methyl-amphetamine (see recipe under METHYL-DMA) in 30 mL glacial acetic acid there was added, dropwise and with good stirring, a solution of 5.5 g bromine in 15 mL acetic acid. The reaction became quite warm, and turned very dark. After stirring an additional 45 min, the mixture was poured into 200 mL H2O and treated with a little sodium hydrosulfite which lightened the color of the reaction. There was added 20 mL concentrated HCl, and the reaction mixture was washed with 2x100 mL CH2Cl2 which removed most of the color. The aqueous. phase was made basic with 25% NaOH, and extracted with 3x100 mL CH2Cl2. The removal of the solvent from the pooled extracts under vacuum gave 1.8 g of an oil which was dissolved in 10 mL IPA, neutralized with concentrated HCl, and diluted with 100 mL anhydrous Et2O. No crystals were obtained, but rather an oily and somewhat granular insoluble lower phase. The Et2O was decanted, and the residue washed by grinding up under 3x100 mL Et2O. The original decanted material was combined with the three washes, and allowed to stand for several h. The product 4-bromo-2,5-dimethoxy-N-methylamphetamine hydrochloride (METHYL-DOB) separated as fine white crystals which weighed, after filtering and air drying, 0.3 g and had a mp of 149-150 °C. The Et2O-insoluble residue finally set up to a pale pink mass which was finely ground under a few mL acetone. Filtration and air drying gave a second crop of product as 0.9 g of pale lavender solids, with a mp of 143-145 °C.

DOSAGE: greater than 8 mg.

DURATION: probably rather long.

QUALITATIVE COMMENTS: (with 8.0 mg) At an hour and twenty minutes, I was suddenly quite light headed. An hour later I must say that the effects are real, and generally good. I am spacey--nothing tangible. And a couple of hours yet later I am still aware. My teeth are somewhat rubby, and as things have been pretty steady for the last three hours, this will prove to be long lasting. There are a lot of physical effects that may be kidding me into providing myself some of the mental. At the sixth hour, I find that this is almost entirely physical. My teeth are tight, there is a general physical tenseness, my reflexes seem exaggerated, and my eyes are quite dilated. All of these signs are lessened by the eighth hour, and do not interfere with sleep at the twelfth hour. There is no desire to proceed any further, at least at the present time. Mental (+) physical (++). Next day, slight impression of persistence of toxicity.

(with 10 mg) Nothing psychedelic, but awfully hard on the bod. The next day (24 hours later) I had a severe response to 5 milligrams of psilocybin.

EXTENSIONS AND COMMENTARY: The mention above, of the 10 milligrams of METHYL-DOB followed by 5 milligrams of psilocybin, leads to some interesting speculation. The usual pattern that is seen when two psychedelic drugs are taken too closely together is that the second experience is less effective than would have been expected. This is the property that is called tolerance, and it is frequently seen in pharmacology. The two exposures may be to a single drug, or they may be to two different drugs which usually have some properties in common. It is as if the spirit of the receptor site had become a little tired and needed a while to rest up and recuperate. When there is a demand for a repeat of full effectiveness, the user will customarily increase the dosage of the drug that is used. It is one of the built-in protections, in the area of psychedelics that, after one experience, you must wait for a period of time to lose the refractoriness that has set in.

The measure of the degree of tolerance that can be shared between different drugs, called cross-tolerance, can be used as an estimate of the similarities of their mechanisms of action. In other words, if A and B are somehow seen by the body as being similar, then a normally effective dose of A will make a next-day's normally effective dose of B weaker than expected. Or not active at all. And B will do the same job on A. If two drugs are different in their ways of doing things in the body, there is most often no cross-tolerance seen. This was described for MDMA and MDA, and is the basis of the argument that they act by distinctly separate mechanisms. A person who used what would be held as an active dose of MDMA for several days lost all response to the drug. He was tolerant to its effects. But an exposure to an effective dose of MDA at the time that tolerance to MDMA was complete, provided a normal response to the MDA. The drugs are not cross-tolerant and the body recognizes them as distinct individuals.

But for one drug to promote, or to exaggerate, the effect of another is called potentiation, and can be a clue to the dynamics going on in the brain or body. Here, admittedly in only a single report, METHYL-DOB had somehow sensitized the subject to a rather light dosage of psilocybin. But there have been other reports like this that I have heard of, from here and there. I have been told of an experiment with the dextro-isomer of DOM (this is the inactive optical isomer) at a level that was, not surprisingly, without any effects. The researcher had a severe reaction the following day with what was referred to as "poor" hashish. A similar form of potentiation has been commented upon under the recipe for TOMSO, where an inactive drug, and a most modest amount of alcohol, add together to create an unexpectedly intense intoxication. But note that in each of these cases, it is a phenethylamine interacting with a non-phenethylamine (psilocybin is an indole, hashish is a non-alkaloid terpene thing, and alcohol is, well, alcohol).

The bottom line with METHYL-DOB is, as with the other N-methylated psychedelics, that it is way down in potency, and probably not worth pursuing.


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