Anandamide §History Anandamide was isolated and its structure first described in 1992 by W. A. Devane, Lumír Hanuš et al. who were working in a team led by Raphael Mechoulam at the Hebrew University of Jerusalem. §Physiological functions Anandamide has been shown to impair working memory in rats. Studies are under way to explore what role anandamide plays in human behavior, such as eating and sleep patterns, and pain relief. Anandamide is also important for implantation of the early stage embryo in its blastocyst form into the uterus. Anandamide plays a role in the regulation of feeding behavior, and the neural generation of motivation and pleasure. A study published in 1998 shows that anandamide inhibits human breast cancer cell proliferation. Some studies have linked anandamide release as a mechanism of analgesic effects induced by exercise, particularly by running. In 1996, researchers discovered anandamide in chocolate. §Synthesis and degradation §See also
Dimethyltryptamine History Another historical milestone is the discovery of DMT in plants frequently used by Amazonian natives as additive to the vine Banisteriopsis caapi to make ayahuasca decoctions. Biosynthesis Biosynthetic pathway for N,N-dimethyltryptamine This transmethylation mechanism has been repeatedly and consistently proven by radiolabeling of SAM methyl group with carbon-14 (14C-CH3)SAM). Evidence in mammals In 2013, researchers first reported DMT in the pineal gland microdialysate of rodents. A study published in 2014 reported the biosynthesis of N,N-dimethyltryptamine (DMT) in the human melanoma cell line SK-Mel-147 including details on its metabolism by peroxidases.  In a 2014 paper, a group first demonstrated the immunomodulatory potential of DMT and 5-MeO-DMT through the Sigma-1_receptor of human immune cells. INMT Endogenous DMT The first claimed detection of mammalian endogenous DMT was published in June 1965: German researchers F.
Tetrahydrocannabinol Tetrahydrocannabinol (THC) is the active chemical in cannabis and is one of the oldest hallucinogenic drugs known. There is evidence that cannabis extracts were used by the Chinese as a herbal remedy since the first century AD. Cannabis comes from the flowering tops and leaves of the hemp plant, Cannabis sativa (shown in the picture on the right). Cannabis contains approximately 60 different psychoactive chemicals called cannabinoids, of which the most important one is tetrahydrocannabinol (THC). The cannabinoids belong to a class of chemicals called terpenoids, meaning terpene-like. THC as an Illegal Drug The cannabinoids are basically non-polar molecules, with low solubility in water, so they are normally self-administered by smoking. Medical Uses Apart from the recreational uses and abuses, THC does have some medical uses. References: Organic Chemistry, Morrison and Boyd (Allyn and Bacon, 1983).
Cannabinoid Synthetic cannabinoids encompass a variety of distinct chemical classes: the classical cannabinoids structurally related to THC, the nonclassical cannabinoids (cannabimimetics) including the aminoalkylindoles, 1,5-diarylpyrazoles, quinolines, and arylsulphonamides, as well as eicosanoids related to the endocannabinoids. Cannabinoid receptors Cannabinoid receptor type 1 CB1 receptors are found primarily in the brain, more specifically in the basal ganglia and in the limbic system, including the hippocampus. They are also found in the cerebellum and in both male and female reproductive systems. Cannabinoid receptor type 2 CB2 receptors are predominantly found in the immune system, or immune-derived cells with the greatest density in the spleen. Phytocannabinoids Cannabis-derived cannabinoids The classical cannabinoids are concentrated in a viscous resin produced in structures known as glandular trichomes. Types Tetrahydrocannabinol Length
Psilocybin Psilocybin[nb 1] (/ˌsɪləˈsaɪbɪn/ SIL-ə-SY-bin) is a naturally occurring psychedelic compound produced by more than 200 species of mushrooms, collectively known as psilocybin mushrooms. The most potent are members of the genus Psilocybe, such as P. azurescens, P. semilanceata, and P. cyanescens, but psilocybin has also been isolated from about a dozen other genera. As a prodrug, psilocybin is quickly converted by the body to psilocin, which has mind-altering effects similar (in some aspects) to those of LSD, mescaline, and DMT. In general, the effects include euphoria, visual and mental hallucinations, changes in perception, a distorted sense of time, and spiritual experiences, and can include possible adverse reactions such as nausea and panic attacks. History Early Modern Albert Hofmann (shown here in 1993) purified psilocybin and psilocin from Psilocybe mexicana in the late 1950s. Occurrence
Cannabis Vault : Chemistry Cannabis Chemistryby Erowid THC Material Safety Data Sheet (Occupational Health Services) Tropane alkaloid Tropane alkaloids are a class of bicyclic [3.2.1] alkaloids and secondary metabolites that contain a tropane ring in their chemical structure. Tropane alkaloids occur naturally in many members of the plant family Solanaceae. Some tropane alkaloids have pharmacological properties and can acts as anticholinergics or stimulants. Anticholinergics Anticholinergic drugs and deliriants: All three acetylcholine-inhibiting chemicals can also be found in the leaves, stems, and flowers in varying, unknown amounts in Brugmansia (Angel Trumpets or Devil's Weed), a relative of Datura. Stimulants Stimulants and cocaine-related alkaloids: Cocaine, from Erythroxylum cocaEcgonine, a precursor and metabolite of cocaineBenzoylecgonine, a metabolite of cocaineHydroxytropacocaine, from Erythroxylum cocaMethylecgonine cinnamate, from Erythroxylum coca Others Non-natural tropanes There exist some synthetic analogs of tropane alkaloids, see Phenyltropanes See also
Lysergic acid diethylamide Lysergic acid diethylamide, abbreviated LSD or LSD-25, also known as lysergide (INN) and colloquially as acid, is a semisynthetic psychedelic drug of the ergoline family, well known for its psychological effects which can include altered thinking processes, closed- and open-eye visuals, synesthesia, an altered sense of time and spiritual experiences, as well as for its key role in 1960s counterculture. It is used mainly as an entheogen, recreational drug, and as an agent in psychedelic therapy. LSD is non-addictive, is not known to cause brain damage, and has extremely low toxicity relative to dose. However, acute adverse psychiatric reactions such as anxiety, paranoia, and delusions are possible. LSD was first synthesized by Albert Hofmann in 1938 from ergotamine, a chemical derived by Arthur Stoll from ergot, a grain fungus that typically grows on rye. Effects Physical LSD can cause pupil dilation, reduced or increased appetite, and wakefulness. Psychological Sensory Potential uses
The Endocannabinoid System: An Osteopathic Perspective The endocannabinoid system was discovered long after the endorphin system, which was indirectly detected in 1801 when morphine sulfate was isolated from opium. Morphine's mechanism of action remained a mystery until the opioid μ receptor was identified. That discovery begged the question: Why do humans express a receptor for an opium poppy (Papavera somniferum) plant compound? In 1897, Andrew Taylor Still, MD, DO,2 the founder of osteopathic medicine, famously stated, “Man should study and use the drugs compounded in his own body.” Since then, research—particularly osteopathic medical research—has redirected its attention from the endorphin system to the endocannabinoid system.4-10 A search on the National Library of Medicine's PubMed database of endorphin in the 1992 literature, the year endocannabinoids were discovered, returns 596 citations, whereas endocannabinoid yields only two citations. Exogenous Cannabinoids Animal studies of THC began immediately after its discovery. Figure 1.
Nicotine In smaller doses (an average cigarette yields about 1 mg of absorbed nicotine), the substance acts as a stimulant in mammals, while high amounts (50–100 mg) can be harmful. This stimulant effect is likely to be a major contributing factor to the dependence-forming properties of tobacco smoking, nicotine patches, nicotine gum, nicotine inhalers and liquid nicotine vaporizers. According to the American Heart Association, nicotine addiction has historically been one of the hardest addictions to break, while the pharmacological and behavioral characteristics that determine nicotine addiction are similar to those determining addiction to heroin and cocaine. The nicotine content of popular American-brand cigarettes has slowly increased over the years, and one study found that there was an average increase of 1.78% per year between the years of 1998 and 2005. Psychoactive effects Medical uses A 21 mg patch applied to the left arm. Side effects
Melatonin Melatonin The hormone can be used as a sleep aid and in the treatment of sleep disorders. It can be taken orally as capsules, tablets, or liquid. It is also available in a form to be used sublingually, and there are transdermal patches. Discovery Biosynthesis Melatonin biosynthesis involves four enzymatic steps from the essential dietary amino acid tryptophan, which follows a serotonin pathway. In bacteria, protists, fungi, and plants melatonin is synthesized indirectly with tryptophan as an intermediate product of the shikimic acid pathway. Regulation In vertebrates, melatonin secretion is regulated by norepinephrine. It is principally blue light, around 460 to 480 nm, that suppresses melatonin, proportional to the light intensity and length of exposure. Animals In vertebrates, melatonin is produced at nighttime by the pineal gland, a small endocrine gland located in the center of the brain but outside the blood–brain barrier. Plants Functions
Science for potheads: Why they love to get high Drug warriors have long tried to smear marijuana as a dangerous scourge, seeking to criminalize possession of a leaf they clearly do not understand. The key to comprehending its effects is by better grasping our physiology. Marijuana is not magic. Marijuana (botanical name, cannabis) affects the human body because the plant-based cannabinoids in marijuana, once ingested, can “plug into” the cannabinoid receptors that are used by the cannabinoids made by our own bodies. It’s not just people that have cannabinoid systems. Evolution has selected for cannabinoid systems, meaning once they emerged, they were retained, and broadly adopted. The cannabinoid receptor seems to have first appeared approximately 600 million years ago in sea squirts. A sea squirt is a tunicate, and tunicates contain a host of potentially useful chemical compounds that are effective against various types of cancer. Could that underlying mechanism allowing for “reprogramming” involve the cannabinoid system?