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Ketamine is a fast-acting, dissociative anesthetic. Unlike traditional anesthetics, it works by essentially “cutting off” the brain from the body. With no external stimulation being delivered to the brain from the nervous system, perception increases to fill the gap left by the missing senses giving rise to a hallucinogenic state also known as the emergence phenomena.

The effects of ketamine vary with the dosage level and method of administration. At lower dosages the effects are mildly hallucinogenic and slightly stimulating. This type of use is often found at clubs and raves and lends itself well to insufflation or snorting. At higher dosages, especially those administered intramuscularly, the effects tend to be more overwhelming. Although descriptions vary greatly, many users talk about alternate planes of existence, a sense of oneness with everything, expansion in awareness of time and new understandings of the fabric of reality and existence. Communication becomes difficult and movement can be nearly impossible. The trip usually lasts about an hour for an intramuscular dose.

Ketamine was first discovered in 1961. By 1970 it was designed as an improved version of phencyclidine (PCP.) It afforded physicians and surgeons a “safe and potent, intravenously administered anesthetic of short duration which combined analgesic and sleep-producing effects without significant cardiovascular and respiratory depression." Somewhat out of favor today, when ketamine is used on humans it is usually confined to children, the elderly and people in so-called third-world countries because of the emergence phenomena.

When used recreationally ketamine can come in powder, tablet or liquid form and can be administered orally, rectally, by insufflation (snorting,) intramuscularly or intravenously. Intravenous use of ketamine is not recommended for recreational users. The main reason for this is that the onset of Intravenous ketamine can occur so rapidly and be so overpowering that a user can be rendered unconscious before even removing the needle.

At higher dosage levels, ketamine should only be used in a safe environment and with a clear-headed sitter whenever possible.

Using Ketamine

The primary medical use of ketamine is as an injectable anesthetic, but in sub-anesthetic doses it produces a profound, dissociative effect also known as an “emergent” state or the emergence phenomena. This state is often labeled ego-loss by sers and is described similar to accounts of out-of-body or near-death experiences.

Taken intramuscularly (IM,) ketamine comes on quickly with an initial onset of about two minutes. Insufflated ketamine doses come on slower at 5 – 10 minutes and oral doses slower still at closer to 15 – 20. IM doses to last about an hour and oral doses up to 2 – 3. The first feelings of ketamine are a warmish, all-over body tingle and a sense of relaxation. From there the effects grow in waves or K-waves as they’re often called. Taken intramuscularly, ketamine will be in full effect by the 10 minute mark. IM ketamine peaks at 12 – 25 minutes and holds steady for another 20. At the height of a ketamine trip a person will feel completely removed from their body and surroundings. Descriptions of the ketamine peak experience vary widely but often include alternate planes of existence, dazzling insights, powerful hallucinations, communication with various entities, a sense of oneness and connectedness and a merging of past, present and future. During a ketamine trip it can be extremely difficult, if not impossible, to communicate. Walking or moving around in general can be nearly impossible and is not recommended. To the outside observer, ketamine users will seem to fall into a deep trance state. Having a sober sitter around who is familiar with the effects of ketamine can be highly beneficial. The comedown off ketamine happens gently but rapidly once it’s begun.

Though the ketamine experience can be on par with other powerful psychedelics such as LSD and mushrooms, many users find there is less potential for fear or a bad trip. Also, ketamine lasts nowhere near as long as LSD or mushrooms, so in the rare case of an unpleasant trip one is never far from coming out the other side. One of the most commonly reported side effects of the ketamine experience is a decreased fear of death.

Ketamine dosage depends on method of administration. Food should not be consumed 90 minutes prior to ketamine use and should be avoided for longer if possible as nausea and vomiting are possible if uncommon. Dosages and reactions vary greatly from person to person.

Producing Ketamine

Ketamine is a synthetic chemical. A synthesis is complicated and should be attempted only by a competent and experienced chemist.

Ketamine is more difficult to synthesize than the previously considered PCP derivatives. Although it is currently a popular and common drug on the illicit market, it is obtained exclusively by diversion of commercial sources rather than synthesis. This route has an overall yield of ~60%, with a difficulty rating of 2-3 out of 10 and a hazard rating of 1-2 out of 10. The general necessity of producing anhydrous methylamine in a clandestine setting, rather than purchasing it, increases the difficulty. Use of propylamine rather than methylamine would simplify this reaction, as its boiling point is above room temperature vs. methylamine, which is a gas at room temperature.

The synthesis starts with the reaction of cyclopentyl Grignard and o-chlorobenzonitrile to give o-chlorophenyl-cyclopentyl ketone, followed by alpha bromination of the ketone, and then reaction with methylamine to form an alpha-hydroxy imine (1-Hydroxycyclopentyl-(o-chlorophenyl)-ketone-N-methylimine). Heating this imine results in ketamine via a novel alpha-hydroxyimine rearrangement (refs. 20, 21, 22, 23, 24 ). Overall yields are ~60%.

Synthetic Procedure for Ketamine Synthesis

Step 1: (o-chlorophenyl)-cyclopentyl ketone 119.0 g of cyclopentyl bromide and 19.4 g of magnesium are reacted in ether or THF to give a cyclopentyl Grignard reagent. The best yields are obtained if the ether solvent is distilled from the Grignard under vacuum and replaced with hydrocarbon solvent, such as benzene. 55.2 g of o-chlorobenzonitrile is then added to the reaction mixture and stirred for three days. The reaction is then hydrolyzed by pouring it onto a mixture of crushed ice and ammonium chloride, containing some ammonium hydroxide. Extraction of the mixture with organic solvent gives o-chlorophenylcyclopentylketone, bp 96-97 C (0.3 mm Hg) (CAS# 6740-85-8).

Step 2: alpha-bromo (o-chlorophenyl)-cyclopentyl ketone To 21.0 g of the above ketone is added 10.0 g of bromine in 80 ml of carbon tetrachloride dropwise at 0 deg. C. After all of the Br2 has been added, an orange suspension forms. This is washed with a dilute aqueous solution of sodium bisulfite and evaporated to give 1-bromocyclopentyl-(o-chlorophenyl)-ketone, bp 111-114 C (0.1 mm Hg). Yield is ~66%. This bromoketone is unstable and must be used immediately. Also attempts to distill it at 0.1 mm Hg lead to some decomposition, so it should be used without further purification.

The bromination may also be carried out with N-bromosuccinimide in somewhat higher yields (~77%).

Step 3: 1-hydroxycyclopentyl-(o-chlorophenyl)-ketone-N-methylimine 29.0g of above bromoketone is dissolved in 50 ml of liquid methylamine freebase. Benzene may also be used as solvent. After one hour, the excess liquid methylamine is allowed to evaporate, although increasing the reaction time to 4-5 days may increase yield. The residue is then dissolved in pentane and filtered. The solvent is evaporated to yield 1-hydroxy-cyclopentyl-(o-chlorophenyl)-ketone N-methylimine, mp 62 C (yield ~84%).

Step 4: 2-Methylamino-2-(o-chlorophenyl)-cyclohexanone (ketamine) The final step is a thermal rearrangement, and gives almost quantitative yield after 180 C for 30 min. An alternative to the use of decalin as solvent in this step is to use a pressure bomb.

2.0 g of the preceding N-methylimine is dissolved in 15 ml of decalin and refluxed for 2.5 h. After evaporation of the solvent under reduced pressure, the residue is extracted with dilute hydrochloric acid, the solution treated with decolorizing charcoal, and the resulting acidic solution is made basic. The liberated product, 2-methylamino-2-(o-chlorophenyl)-cyclohexanone (ketamine), after recrystallization from pentane-ether, has a mp of 92-93C. The hydrochloride has a mp of 262-263 C.

As with PCE, the freebase is too caustic to be smoked, and must be converted into the HCl salt in order to be consumed in this manner.