A cactus is a member of the plant family Cactaceae. Most cacti live in habitats subject to at least a certain amount of drought. Cacti show many adaptations to conserve water. Most species of cacti have lost true leaves, retaining only spines, which are highly modified leaves. As well as defending against herbivores, spines help prevent water loss by reducing air flow close to the cactus and providing some shade. Cacti occur in a wide range of shapes and sizes.
Peyote and Mescaline
A number of species of cacti have been shown to contain psychoactive agents, chemical compounds that can cause changes in mood, perception and cognition through their effects on the brain. They served in Middle American cultures, like the Aztec one, as keys to knowledge withheld from men in their normal minds, the keys to Extra-sensory Perception, the Mediators (as the Indians believed) between men and their gods. These plants were hallucinogens, psychotropic agents.
Two species have a long history of use by the indigenous peoples of the Americas: peyote in North America, and the San Pedro cactus in South America. Both contain mescaline.
Mescaline or 3,4,5-trimethoxyphenethylamine is a naturally occurring psychedelic alkaloid of the phenethylamine class, known for its hallucinogenic effects similar to those of LSD and psilocybin. It shares strong structural similarities with the catecholamine dopamine.
Mescaline is biosynthesized from tyrosine or a hydroxylated phenylalanine.
Mescaline's hallucinogenic properties stem from its structural similarities with dopamine and serotonin. In plants, this compound may be the end product of a pathway utilizing catecholamines as a method of stress response, similar to how animals may release compounds such as cortisol when stressed. The in vivo functions of catecholamines have not been investigated, but they may function as antioxidants and as integral cell wall components that resist degradation from pathogens. The deactivation of catecholamines via methylation produces alkaloids such as mescaline.
Mescaline acts similarly to other psychedelic agents. It binds to and activates the serotonin 5-HT2A receptor with a high affinity. How activating the 5-HT2A receptor leads to psychedelia is still unclear, but it is likely to involve, somehow, excitation of neurons in the prefrontal cortex. Mescaline is also known to bind to and activate the serotonin 5-HT2C receptor.
Serotonin (5-HT) is a monoamine neurotransmitter derived from the amino acid tryptophan. In the CNS, all serotonergic neurons originate from the raphe nuclei and project diffusely to many areas in the brain. This ancient pathway is important for modulating complex behaviours like aggression, anxiety, appetite, knowledge, learning, memory, mood, nausea, sleep, thermoregulation. The vast majority of hallucinogenic substances highjack this pathway, acting as 5-HT receptor agonists. In particular, the 5-HT2A subtype seems to be especially important for mediating the hallucinogenic effects of many drugs, like mescaline and LSD. 5-HT2A is a subtype of one of the seven classes of serotonin receptors.
This receptor is not linked with an ion channel, but is instead associated with a trimeric G-protein complex (α, β, & γ subunits). When serotonin binds to 5-HT2A the receptor undergoes a conformation change that is translated to its cytosolic region. A bound GDP dissociates from the α subunit, and is replaced by GTP. This actively causes the separation of the Gq from the β/γ complex, and initiates the activation of membrane bound phospholipase C (PLC). When activated PLC cleaves phosphatidylinositol-4,5-bisphosphate (PIP2) into inositol-1,4,5-triphosphate (IP3) and diacyglycerol (DAG). The products of this cleavage are responsible for two distinct cellular mechanisms. DAG activates protein kinase C (PKC), which can lead to the activation of mitogen activated protein kinase (MAPK) and the activation of transcription factors like CREB. At the same time, IP3 causes the release of intracellular calcium, thereby activating calmodulin and other cytosolic proteins. These effects are known to also activate CREB.
Activation of 5-HT2A receptors on excitatory deep cortical layer neurons stimulate the release of glutamate. Input from both glutimatergic and serotonergic neurons synapse on layer V pyramidal cells in the prefrontal cortex, where they facilitate the activation of CREB and release of growth factors like BDNF. Mescaline induces a superactivation of this pathway and this situation seems to cause a complete distortion of the normal neuroendocrine equilibrium.
The effects of mescaline, if it is ingested, begin to appear 45-120 minutes after consumption, depending on the content of the stomach. In the initial phase it is not rare to witness nausea and vomit, which disappear within an hour, replaced by great salivation, accompanied by a weakening or disappearance of feelings of hunger, tiredness and thirst. An acceleration of pulse and increment of blood pressure can be observed.
After 45 minutes / 2 hours from the beginning of the effects (depending on dosage and purity of the substance) a second phase follows, characterised by sensorial hallucinations (visual, auditory, tactile and olfactory) and amplification of the senses. Generally the experience lasts between 4 and 8 hours, but with particularly high dosages some cases have been reported of experiences lasting over 24 hours. When the effect disappears, feelings of tiredness and physical and mental exhaustion can be perceived. Other physical effects may include pupil dilation.
Like many other hallucinogens, mescaline brings about alterations of visual and sensorial perception. However, compared to other types of drugs, the psychological effects of psychedelics are more polyhedric and less certain: within the same experience, there can occur loss of awareness of time and space, difficulty of expression, loss even permanent, for short periods, of long- or short-term memory (rare), visions, synesthesia, euphoria, feelings of peace and well-being, perception of greater depth of thought, sensations defined "otherworldly", empathy towards surrounding people, animals, plants or objects, but also, in the case of real negative events, and their consequent amplification, anxiety, panic and transitory states of paranoia or delirium. A subject affected by effects of this latter kind should be quietly comforted, tranquilized and left alone in a dark, safe and ventilated place until the end of the effects.
Mescaline has a wide array of suggested medical usages, including treatment of alcoholism and depression. However, its status as a Schedule I controlled substance in the Convention on Psychotropic Substances limits availability of the drug to researchers. Because of this, very few studies concerning mescaline's activity and potential therapeutic effects on humans have been conducted since the early 1970s.
Cactus Grandiflorus and Hordenine
It is necessary to emphasise that fat plants do not possess only hallucinogenic properties. An example of this is Cactus grandiflorus. This fat plant's activity is determined in particular by a group of active principles known as cactine and hordenine.
Pathogenic experimentation and clinical observation confirm that cactus grandiflorus exerts a constrictive action on muscle fibres, smooth and striated, but especially:
on the cardiovascular apparatus,
on the digestive apparatus,
on the urogenital apparatus.
Hordenine is biosynthesized by the step-wise N-methylation of tyramine, which is first converted to N-methyltyramine, and which, in turn is methylated to hordenine.
Results of some experiments in pharmacological models show that hordenine is an adrenergic drug with indirect action. It doesn't directly stimulate the nervous system and encourage the release of norepinephrine but it liberates norepinephrin from stores. In isolated organs and those structures with reduced epinephrine contents the hordenine-effect is only very limited.
Experiments on intact animals (rats, dogs) show that hordenine has a positive inotropic effect upon the heart, increases systolic and diastolic blood pressure, peripheral blood flow volume, inhibits gut movements but has no effect upon the psychomotoric behaviour of mice. All effects have short duration, and only occur after the administration of high dosages.
Like other monoamines, hordenine is metabolized by monoamine oxidases (Hordenine was found to be a selective substrate for MAO-B, from rat liver. It was not de-aminated by MAO-A from rat intestinal epithelium).
An excessive accumulation of hordenine can cause relevant hypertension problems.
Pharmacological effects of hordenine