Drugs from Nature (Natural Doesn't Mean Safe) PDF

Drugs from Nature (natural doesn't mean safe) Herbal remedies are sometimes described as a "safe" alternative to prescription medications because they are from nature. However, some of the deadliest toxins are also "natural", like botulinum toxin. This section highlights drugs that are psychoactive...

Drugs from Nature (natural doesn't mean safe) Herbal remedies are sometimes described as a "safe" alternative to prescription medications because they are from nature. However, some of the deadliest toxins are also "natural", like botulinum toxin. This section highlights drugs that are psychoactive (affecting brain function) and can also be abused and contribute to serious health problems. It ends with a brief discussion of natural products that are hallucinogens, derived from mushrooms, cactus, and plant leaves. 1. Alcohol Humans have been producing and consuming ethanol (alcohol) for thousands of years, and as such our physiology is likely adapted to modest consumption of alcohol. Indeed, fermented cider was a safer beverage than tap water in the 1800's, before sanitation. However, alcohol is often abused, and chronic alcoholism causes a list of health problems in addition to its addictive properties. Alcohol mechanism of action Ethanol is the product of yeast metabolism, in which complex carbohydrates and sugars from grains are used as an energy source. Alcohol is a very small molecule compared to other drugs: just two carbons and a hydroxyl group. The carbon part of alcohol is not charged, so it passes easily through fats and cell membranes - that enables alcohol to rapidly move from the stomach to the blood and from the blood into the brain. The hydroxyl group (OH) gives alcohol a weak negative charge, so that it is also very soluble in water. Alcohol is an agonist at GABA-A receptors. It acts in a manner that is similar to barbiturates to keep the channel open longer. This allows more chloride into the neuron, so the neuron is hyperpolarized and less likely to fire. Alcohol is also an antagonist at NMDA receptors, which are receptors for the main excitatory neurotransmitter in the brain, glutamate. Like GABA channels, NMDA receptors are also ion channels, but importantly they allow sodium and calcium into the neuron. This means that NMDA receptors will promote neuron activation. Since alcohol blocks the NMDA receptor, it prevents glutamate from activating the neuron and causing it to fire. Therefore, alcohol is a powerful depressant of neurons throughout the brain because it blocks the excitatory message of glutamate and it amplifies the inhibitory message of GABA. Alcohol effects on the body Alcohol has different effects on the body depending on the dose. As the level of alcohol rises, more neurons are depressed. The different stages of alcohol intoxication are due to greater and greater quieting of neurons. The first neurons to become quiet include the ones that normally keep dopamine neurons from firing. Therefore a low dose of alcohol will cause dopamine neurons to fire more. This contributes to the feeling of well- being (high) and also explains why alcohol is addictive. Another brain region that is affected at low doses is the amygdala. Amygdala neurons are easily quieted by alcohol and anxiety is reduced. At the same time, neurons in the cortex are less active, and there is less behavioural inhibition. This causes people to do or say things that they would not otherwise do. Motor coordination is also impaired, and this is due to the actions of alcohol on the cerebellum. Acute alcohol poisoning causes motor impairment, amnesia, vomiting, loss of consciousness, breathing suppression, coma, and can be fatal. Once alcohol is absorbed in the body there is no medicine to counteract its actions, and supportive measures (for example to regulate breathing and body temperature) are used to prevent death. 2. Nicotine Nicotine from tobacco smoke is considered one of the most highly addictive substances for humans. Tobacco plants produce nicotine as a natural pesticide. Nicotine's effects on humans depend on the dose. Low doses elicit a feeling of serenity, reducing agitation. At the same time, low doses of nicotine increase attention and focus. However, higher doses cause nausea and vomiting. It is also a poison to humans, and tobacco field workers can become ill from overexposure to nicotine. It causes vomiting, delirium, difficulty breathing, and excessive mucous production. In toxic doses it slows the heartbeat and breathing, makes muscles very weak, and can cause seizures. Nicotine poisoning can be serious if a child or pet eats a cigarette, or if liquid nicotine (used in vaping) is spilled on the skin. Nicotine mechanism of action Nicotine acts as an agonist of the nicotinic acetylcholine receptor. These are ion channels that allow sodium into the neuron. Because they allow sodium in, they are excitatory and will promote neuron firing. Therefore, nicotine promotes the firing of neurons that have the nicotinic receptor. Nicotine receptors are located in the thalamus, the cortex and the basal ganglia in the brain. Their presence on dopamine neurons is the reason why nicotine is addictive. In the body nicotinic receptors are located at the neuromuscular junction. The neuromuscular junction is the place where neurons connect to our muscles to control all of our voluntary movements. The other place where nicotinic receptors are located is in the neurons that make up the autonomic nervous system. This is why smoking or consuming nicotine and activating the nicotinic receptors can cause nausea and vomiting. Nicotine effects on the body Nicotine is a very potent poison and can be lethal at doses of 50 milligrams (one cigarette delivers 1 milligram of nicotine. Nicotinic receptors are located at the neuromuscular junction - when they are activated they cause the muscle to move. However, when the nicotinic receptors are continually activated (by excessive nicotine poisoning), the receptors actually stop working. They become desensitized and the muscle becomes flaccid. This is what causes the muscle weakness and shallow breathing from nicotine poisoning. Fortunately, most people consume nicotine at doses that are much too low for these effects. At the doses that are delivered by cigarettes (or e-cigarettes), nicotine activates receptors in the brain that lead to increased dopamine neuron firing, and increased focus and attention. Although nicotine causes increased heart rate and blood pressure, its actions on the brain cause the person to feel calmer. Smoking is the primary cause of lung cancer and chronic obstructive pulmonary disease, and chewing tobacco is associated with increased rates of mouth cancer. Smoking also causes hardening of the arteries and increases the risk for heart attack and stroke. The addictive nature of nicotine in the tobacco is the reason why people continue to smoke even after they are diagnosed with a serious disease. 3. Cocaine Cocaine is purified from coca leaves that grow in South American countries (Colombia, Peru, Bolivia, and Ecuador). Although it is not used medicinally in North America, the leaves are brewed to make a tea for headaches. It is also an effective local anaesthetic and was used for this purpose in dentistry before the development of lidocaine (which has a similar structure to cocaine). There is evidence that indigenous people have consumed coca leaves for thousands of years as remains of coca leaves have been found alongside mummies uncovered in South America. Cocaine mechanism of action As discussed in the chapter on attention, cocaine blocks the actions of the dopamine transporter, causing dopamine levels to accumulate in the synapse. Cocaine also acts on the norepinephrine transporter and the serotonin transporter, so those neurotransmitters are also increased by cocaine. Cocaine acts as a local anaesthetic through a different mechanism. Cocaine (and lidocaine) block the sodium channels that open during an action potential. They are anaesthetic because they prevent the nociceptive sensory neuron, and other sensory neurons, from firing. This is achieved at a much higher dose than what is consumed by snorting, smoking, or injecting cocaine. Cocaine effects on the body Cocaine is a stimulant, increasing the level of alertness and arousal. It is also a psychomotor stimulant, and people often want to run after taking it. It induces a state of euphoria and people experience grandiose thoughts or experience paranoia. Cocaine increases the heart rate and blood pressure, and chronic cocaine use greatly increases the risk of heart attack and stroke. Although not all people who use cocaine will become addicted, cocaine addiction is very difficult to treat and has a high relapse rate. 4. Hallucinogens Serotonergic drugs There are a number of natural products that are hallucinogenic. Hallucinations can be caused by specifically activating the 5HT2A serotonin receptors in the brain. Drugs like psilocybin (from a specific strain of mushrooms) and mescaline (from peyote cactus) activate 5HT2A receptors and induce vivid hallucinations. These compounds lose their hallucinogenic properties when people are given a drug that blocks the 5HT2A receptor. This is strong evidence that hallucinations occur because the drugs activate the 5HT2A receptor. The synthetic hallucinogen LSD acts by the same mechanism. These hallucinogens (psilocybin, mescaline, and LSD) were investigated in the 1950’s and 60’s for their ability to induce an altered state of consciousness and as potential treatments for drug addiction, anxiety, and depression. However, they became connected with a counterculture social movement and received little attention from medical researchers from 1970 – 2015. They were listed as “Schedule 1” drugs by the U.S. Drug Enforcement Agency, which means that they had no medical purpose and a high likelihood for abuse or addiction. Listing these drugs as Schedule 1 made it difficult to obtain these medicines for research, which was unfortunate. These drugs actually have low abuse potential and recent evidence suggests that they may be beneficial for the treatment of PTSD, anxiety, and depression. The principle adverse effects of drugs that activate the 5HT2A receptor or increase serotonin levels (Ecstasy/MDMA) are nausea and vomiting. The other side-effect, which can be life-threatening, is increased body temperature (hyperpyrexia). Kappa agonist salvanorin Another potent hallucinogen is salvanorin A, which is extracted from the salvia divinorum plant. Salvanorin A is reported to be the "most potent naturally occurring hallucinogen" by Dr. Bryan Roth, the researcher who identified its mechanism of action. His laboratory discovered that it is a very selective agonist of the kappa opioid receptor, meaning that no other receptors have been found to bind the drug. Activation of kappa opioid receptor causes brief but intense hallucinations that can be disturbing. In fact, other drugs that selectively activate the kappa opioid receptor are aversive in animals, meaning they will avoid locations where they were administered the drug.