Mechanism of opioids: Euphoria and the cause of addiction.
Inhibition of Endogenous opioids following prolonged exposure to opioid analgesics.
How treatments help in restoration of endogenous opiate production in the body.
Mechanisms surrounding the impact of Ibogaine on the body.
The neurobiology of Ayahuasca
The potential impact of DMT in improved neurological health
Mechanism of Buprenorphine.
The advent of chronic diseases and the advancement in treatment methods led to the introduction of opiate medications. These were strong analgesics which were very effective in the treatment of severe pain. These drugs, unfortunately, were found to be highly addictive given the euphoric feeling they resulted into after use. This also exacerbated their uses as recreational drugs taken without supervision. In the wake of increased use of these drugs, there have been numerous reports depicting progressively growing death rates over the years making opiate abuse an epidemic needing to be tackled (ASAM, 2016). This has prompted in-depth research on the neurological effects of opiate drugs and their bearing in the causing of drug addiction. This is to find substances that can counteract their effects and possibly help mitigate the high rate of death that has been caused by opiate drug use over the years (Holden, Jeong and Forrest, 2005). There are various treatments that have been discovered and found to help in the rehabilitation of addicts and possible mitigation of the effects brought about by opiate drug overdose. I hypothesize that opioid treatments’ mechanism of operation is remotely similar to that of opioids but with less severe impact which aid in the rehabilitation of opioid drug addicts and can also be used in the treatment of accidental opioid overdose.
Mechanism of opioids: Euphoria and the cause of addiction.
The mechanism of opioids is greatly attributed to the mode in which it is introduced to the body. Prescribed opioids are can be better managed while non-medical use normally increases the risk of addiction. Addiction is usually a result of prolonged use of opioid drugs. It arises from the body’s inherent tendency to depend on a certain substance due to its pleasurable effects in the brain and the rest of the body in general. Opioids are primarily used for the alleviation of pain and it is in achieving thing function that they induce euphoric effects which are so strong and pleasurable that the user will feel the urge to keep using the drugs.
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The process, however, can be attributed to the activity that follows opioid use in a patient’s brain. When one introduces opiate drugs into their body system, it is transported in the blood to the other organs of the body including the spinal cord, the brain, and the gastrointestinal tract. When the molecules of the drugs get to these places, they get attached to specific proteins referred to as opioid receptors or in some cases opiate receptors. This happens in the presynaptic neuron and triggers a flurry of neurochemical activity. This activity involves the synaptic vesicle, the opioids, the opioid receptors, dopamine, dopamine transporters and dopamine receptors.
The body’s normal process usually involves a controlled release of dopamine which usually brings about the ‘feel good effect’ on the body (ASAM, 2016). This is associated with happiness in humans. The ‘feel good effect’ is brought about when the synaptic vesicle releases a certain amount of dopamine and its full effect is achieved when the dopamine is received on the dopamine receptors in the brain (ASAM, 2016). The introduction of opiate drugs into the body alters this process in such a way that it magnifies the ‘feel good effect’ in great proportions leading to an enhanced feeling pleasure and happiness otherwise known as euphoria.
Opiate drugs essentially signal or initiate an increased efflux of dopamine such that the dopamine receptors are flooded with dopamine magnifying the pleasurable effect brought about by this hormone (Przewlocki and Przewlocka, 2001). The prolonged effect of continued use of opiate drugs leads to the body to change its response mechanism following introduction and re-introduction of a new substance in the body constantly. The opioid receptors’ signaling activity is altered and the synapse transported become dependent on opiate drugs to release dopamine in the body. This results in a situation of drug dependence where the body constantly yearns for opiate drugs for its normal functioning. It is following this effect that addiction arises. Addiction is another term for chronic drug dependence.
Inhibition of Endogenous opioids following prolonged exposure to opioid analgesics.
Endogenous opioids also known as opioid peptides are peptides that produce certain hormones that have similar effects as opioids in the body. An example of a hormone produced by opioid peptides is endorphin. The characteristic of having similar effects as opiates automatically brands this the innate pain relieving system in the body. This in effect, also makes it susceptible to replaceability by medical or artificial opioids. The endogenous opioid system produces three types of opioids including dynorphins, beta-endorphins and both the metenkephalin and leuenkephalin (Holden, Jeong and Forrest, 2005). Their functions in the body are to act as neurotransmitters or neuromodulators in the brain such that they initiate the synapse release of the pain-relieving substance also referred to as the analgesia.
These endogenous opioids are normally located at the major opioid receptors in the body including the mu, the delta, and the kappa (Przewlocki and Przewlocka, 2001). The normal functioning of an endogenous opioid is to get attached to these receptors such that they trigger the synaptic vesicle to release hormones responsible for pain relief or production of good feelings in the body. As explained in the process that leads to addiction, opiate medication also acts the same way as endogenous opioids. The only difference is that they are stronger and come with side effects (Holden, Jeong and Forrest, 2005). These effects include euphoria which is an enhanced feeling of pleasure and happiness, nausea and constipation. When the use of opioids increases to a certain point the body’s homeostatic functioning is altered such that increased availability of medical opioids leads the body to reduce the production of endogenous opioids. Consequently, the endogenous opioids are ‘replaced’ in functioning by the medical or abused opioids and given the body’s working mechanism and its requiring endogenous opioids in its functioning; it shifts dependence to the artificial opioids.
As such, the body, through the brain ceases to recognize, detect, or produce endogenous opioids due to the presence of the stronger and readily available medical or abused opioids. Readily available because the inhibition of endogenous opioids is brought about due to the prolonged and constant use of opiate drugs. This effect on the body is what inadvertently leads to addiction and dependence on the opiate drugs to the point that a patient feels sick or unable to perform normally without the drugs. This is what leads to severe withdrawal symptoms. However, another phenomenon, receptors’ signaling mechanism has also been attributed to the withdrawal effect. The continued use of powerful opioid whose intake also increases with time since the body builds endurance to their effects with time causes withdrawal symptoms. This comes about when the body becomes accustomed to the stronger drugs to the point that the weaker endogenous opioids become undetectable or produce very minimal effects to the patient especially when it comes to pain alleviation and production of euphoric effects.
This inhibition effect is normally exacerbated by a certain property of opioid drugs that is tolerance to the user. Prolonged and continued use of opiate drugs have been known to cause the user to develop resistance to the drug. This happens when opioid receptors need more of the drug to produce an effect in the body. This means that an amateur user would require a smaller dose compared to the veteran that has been using for a longer time. The numbing of the receptors to the effects of the drugs is quite like what happens to endogenous opioids and their effect on the body after using the artificial opioids for a longer time. To counter this effect, the user must use a higher dose to get to the normal high as time goes by. Subsequently, the doctor is also forced to prescribe a higher dosage to cure pain a patient. This has been largely the root of the problem. Increased availability has meant higher dosages are being made readily directly contributing to the suppression of endogenous opioid production (Przewlocki and Przewlocka, 2001). The magnitude of this effect grows with usage for a longer time. The body even starts to develop tolerance against the previously stronger dosages even rendering endogenous opioids more useless over time. The result is that a chronic drug user that has been using for a longer time would find it very difficult to drop the habit.
Conversely, legal use of opioid use has had the same effects. When a patient, say, a cancer patient is frequently exposed to the opiates. Their rehabilitation from the drug might have even more devastating effects that continued use. Their refraining from using the drug would lead to reduced tolerance and the changing of the body’s response to the drug. For an addict looking to stop using drugs, a relapse can potentially lead to the loss of life when the body is unable to handle the number of drugs taken. The user, while imagining they need a higher dosage, will use a higher amount of the drug while oblivious to the fact that the body has started recovering from the previous tolerance it had. This results in drug overdoses that have been identified as one of the leading causes of death. Patients with a history of opiate prescriptions also suffer the same fate when they are suffering from severe pain in emergency situations and the doctor is mandated with alleviating the pain. When initial dosages seem not to produce expected effects, the doctor will increase the prescriptions with the reason that the patient might have developed resistance due to tolerance. Since this property cannot be quantified, the doctor must give the dosage incrementally and a simple delayed effect on the patient can be what causes an overdose in the patient. The aspect of the overdose is crucial, especially when discussing the suppression of endogenous opioid production in the body’s system.
Eventually, all these aspects lead to the less desirable effects that have come to be associated with opiate drug use. It is the concern on these effects that has also led to the need for remedies to the eroded endogenous opioid production. The discovery of an appropriate remedy for this one aspect of the opiate drugs is what is needed to finally bring the opiate drug death crises that have been growing exponentially the world over. The use of alternative methods for pain alleviation have been unsuccessful due to the effectiveness of opioids in short term pain treatment. The alternatives have been less effective since they are weaker in treating pain or that they take a longer time. Taking a longer time means the patient must go through the pain while the patient tries to initiate the therapy. This would mean that the whole pain alleviation process is rendered useless. The world has turned to opioid effect treatment as a better strategy for curbing the epidemic. While the mode of operation of suggested opioid drug treatments has been unknown, there have been concerns that come with their fair share of side effects on the body. This has led to the requirement that they are used while taking precautions to make sure they don’t harm the patient in the process of treatment. The exploration of the various ways endogenous opioid production can be restored leads to the highlighting the various treatments of opioid addiction.
How treatments help in the restoration of endogenous opiate production in the body.
There have been great strides made in the research to find various remedies to the less desirable effects of opiate medication. This has come in the wake of concerns about increased used of opioids in the world following increased availability. Opioids prescriptions are being made more extensively now more than ever. The concerns that this has led to corresponding abuse and death have led researchers to seek alternative ways to cure pain or identify ways in which the addictive effects of opioids can be eradicated to make it safer to use eventually. The various remedies that have been suggested as cures to the addictive effects have been associated with being able to restore endogenous opioid production so as to revert the body to its previous normal body functions.
The manner of operation of these treatments have been inconclusive for a while, and their use has been based on the perceived effects they have on people of laboratory specimen. In that regard, there are different studies and continuing studies that are being made on these treatment types. This paper narrows down to three types of treatment that have been popular recent times and continue to grow in status and popularity as possible treatments for opioid dependence and addiction. They have therefore been linked with having the ability to help in the rehabilitation of chronic drug users and even help patients recover from an involuntary opioid overdose.
Tabernathe Iboga is an African Shrub from whose roots Ibogaine is extracted (Winkelman, 2014). Ibogaine was initially used to combat fatigue and hunger in the traditional African Society (Winkelman, 2014). In recent years, Ibogaine has come to be known for its treatment of drug dependence and potential to help opiate drug addicts successfully stop using (Brown, 2013). It is believed that Ibogaine, following its previous use by traditionalists to alleviate hunger and thirst also has effects of reducing the withdrawal effects associated with drug rehabilitation. Ibogaine also reduces the craving for opiate drugs thus helping a patient prime their bodies in preparation for the restoration of endogenous opioid production in the body.
Apart from West Africa, Ibogaine has been reported to have been used in France as a mental and physical stimulant. The substance which has been banned in the United States was used by athletes for mental and physical stimulation making it a suitable doping agent. This made it banned for use by athletes by the Olympic Board (Donnelly, 2011). This substance has been fronted as having the potential to produce stellar results in the treatments of drug addicts. This is because it has been identified as having the power to reduce the severity of the withdrawal symptoms associated with opiate drugs and which usually push a substance abuser to relapse. Previously, the Ibogaine has been used to reduce anxiety and psychotherapy for patients with past occurrences that they wish to get over. The drug has been determined in this regard to help the patient look at the past conflicts objectively and successfully get over those experiences.
The effects of Ibogaine in psychotherapy are multi-tiered and comprise of different stages that may last up to 72 hours (Donnelly, 2011). The advantage of the substance is in the numbing of the cravings for other drugs including cocaine and heroin (Brown, 2013). It is this property that makes the substance a strong candidate for the treatment of Opioid addiction and in some cases overdose. It is also categorized as a psychoactive drug alongside mescaline and DMT. The more of operation of the substance is such that it restrains the craving for an addictive drug for up to two months giving the addict time to seek further and more effective help without high chances of relapse caused by withdrawal symptoms. This would be especially effective given the severity that is usually attached to the withdrawal effects and the mentality of those who decide to let go of the habit and start a better life.
Mechanisms surrounding the impact of Ibogaine on the body.
The mechanism of operation of Ibogaine is largely similar to that of other substances of the same kind and their effects on serotonin transmission in the body. And while not completely serotonin based, certain aspects of another agonist Ayahuasca have been seen in the functioning of Ibogaine. This is mainly because of its activity in the 5HT2 and 5HT3 in conjunction with various neuroreceptors sites that have been linked with opiate drugs reception (Donnelly, 2011). These sites that have been sites before as the opiate drug receptor sites include the mu, the kappa and the sigma opioid receptor sites. This discovery can lead to the premature proposition that Ibogaine in effect acts directly to the opiate receptor sites, possibly by competing with opiate substances and aiding in the restructuring and the regeneration of endogenous opiate producing glands of the brain leading to the restoration of this function after it has been destroyed by increased use of opiate drugs.
Howard Lotsof, a drug addict who had seen the effects of the Ibogaine first hand noted that its effects are not derived from its acting on the opiate receptor sites nor did it have anything to do with serotonin receptors (Winkelman, 2014). His research on the effects of the drug led him to the conclusion that the mode of action of Ibogaine was more regenerative than counteractive to the opiate drugs. It, in fact, had certain reforming and normalization effects on neuro-adaptors that were known to be greatly affected every time the victims used the drugs. This means that it bolsters the body's resolve for reproduction of endogenous opiates by helping the brain regrow or reset the neuro adaptors responsible for that function. This is complemented by the psychological function of the substance to numb or interfere with learning centers associated with previous drug use reducing the psychological influence brought about when an addict recalls the intensity and pleasure that comes when they use the drug. This can extend further to the causal factors that initially contributed to the commencement of drug abuse activities in the first place.
This makes the functioning of this drug two-pronged thus greatly effective in performing this function. For addicts it can help them forget about the events that led to their abusing activities, this can also work for patients whose addiction was initially induced by medical prescriptions helping them forget the root of the chronic pain that led to their being given those prescriptions in the first place.
Ayahuasca is a kind of tea derived from a vine referred to as Banisteriopsis caapi (Winkelman, 2014) The vine is believed to contain monoamine oxidase inhibitors. Another plant believed to contain this is the Psychotria vindis whose leaves have been found to contain N, N-dimethyltryptamine also referred to as DMT (Winkelman, 2014). This substance has been noted to induce a state of semi-conscious or dream-like state coupled with the intense auditory, visual and emotional effects (Thomas, Lucas, Capler, Tupper and Martin, 2013). Recently, the use of this herb or chemical to control substance abuse has been fronted. While its effect on the brain hasn’t been determined by conclusive research, it has been identified as having been used for therapeutic reasons or spiritual enrichment as used in different countries in South America. Recently, it has been fronted as having the potential to be used as a remedy for the dependence on opiate drugs. The effects of the Ayahuasca is however not restricted to opiate drugs only and has also been identified as a remedy for alcohol addiction. This potential arose from the discovery of the long-term health benefits of the Ayahuasca to the regular user. These benefits were categorized as social and health related. Even more notable was the fact that these effects were highly considered beneficial for the improvement of the mental wellness of the user.
An additional benefit of the Ayahuasca is the fact that has no side effects that can be attributed to it. this is especially significant because most treatments for addiction have been controlled following their potentially harmful effects associated with rampant and uncontrolled use. The discovery of this drug was brought about by the increased Amazonian use for spiritual rituals and healing ceremonies (Thomas et al, 2013). This was for the sake of herbal therapeutic reasons and healing for the communities that were known to use the substance frequently. The use of the Ayahuasca spread out with the arrival of tourists in the area and even movement of the original users to other parts of the world. given the inherent benefits attached to it, it was only a matter of time before it was identified as having great benefits to the health of a drug dependent individual. The substance was known to cause less severe and less devastating drug-dependent behavior among the most frequent users of the Ayahuasca. It is important that the effect of this drug be analyzed to correctly determine its impact as a treatment for opioid addiction and overdose.
The neurobiology of Ayahuasca
A pharmacological assessment of Ayahuasca reveals that its main constituents include DMT and a derivative of an alkaloid harmine, harmaline and tetra-hydroharmine. These alkaloids have been known to be reversible inhibitors of the A-type isoenzyme of the monoamine oxidase (Frecska, Bokor and Winkelman, 2016). The most conspicuous component of the Ayahuasca is the presence of DMT known to have hallucinogenic properties that have been identified in the human body. The constituent DMT is also found in other plants and has been categorized together with other endogenous hallucinogens including bufotenin and 5-methoxy-DMT. The exact impact of this component has not been identified especially as regards to the neurological effects and the ensuing influence on the addiction to a drug and reduction of the withdrawal effects. There have however been strong correlations made on the possible association with the sharing of receptors with opiate drugs with less devastating health impacts (Frecska, Bokor and Winkelman, 2016). This is due to the close association with, or the same effects brought about hallucinogenic drugs which are the induction of false perceptions. The Ayahuasca being an addiction agonist drug has also been compared with other agonist drugs as sharing these same receptor sites. This can be the strongest link to the effect in helping addicts successfully improve and stop using the drugs during rehabilitation with less severe withdrawal effects.
The potential impact of DMT in improved neurological health
The impact of DMT has grown to be more significant with increased research on its potential benefits to the brain (Thomas et al, 2013). This effect including brain tissue protection and neuro-regeneration can be the origin of its use as a treatment for opiate drug effects on an individual. DMT has been discovered to be an endogenous agonist of Sig-1R, a component that been strongly linked to the psychedelic effects shown when a DMT carrying substance is used in the body (Frecska, Bokor and Winkelman, 2016). Other substances have also been found to always bind with the Sig-1R and sometimes even having higher affinity to it than the DMT. This correlation can lead to the logical prognosis of its effect when it binds with the Sig-1R as opposed to other drugs that would be more damaging to the brain in general. Another dimension has pointed out to the mental health benefits brought about by the Sig-1R. These same beneficial properties have been seen in DMT to making it the best substance for brain tissue development especially when combined or bonded to the Sig-1R. The Sig-1R promotes neuron survival against stress and immune process regulation. This explains their health benefits to the Amazonian people and their rituals.
In addition, the Sig-1R also helps in the regeneration of neural tissue. The exact function is the regulation of morphogenesis of neuronal cells. This can be conversely translated into the protection of the neuronal tissue against overgrowth or undergrowth. How does this relate to the reduction in the effects of drug abuse on the brain? This substance will reduce neuronal damage and initiate regeneration after increased use of opiate drugs has eroded the brain’s ability to generate endogenous opiates. The mode in which this substance helps in the restoration of endogenous opiate production can be simplified into a process involving the chemicals found in the Ayahuasca. DMT the major constituent will bind with the Sig-1R which has been linked with brain tissue regeneration and whose function is bolstered by binding with DMT since it has the same effects on the brain (Frecska, Bokor and Winkelman, 2016). This coupled with its impact in ensuring brain cell survival and anti-cancer activity in the body give it a strong potential for increased research and the treatment of not just addiction but other causes of chronic pain.
This is an opioid maintenance therapeutic drug. The preference for Buprenorphine over other agonist drugs arose from the challenge that arose from the use of methadone that required addicts to attend clinic daily since the medication is taken daily (Fudala, Jaffe, Dax and Johnson, 1990). Buprenorphine was identified as an agonist that could be administered less than once a day with similar withdrawal effects though mild (Whelan and Remski, 2012). This effect has been found to be more effective in the counteraction of the overdose of opiate drugs. An opposed to Ibogaine which was subsequently banned in the United States, Buprenorphine is categorized as controlled substance referred to as a schedule 3 narcotics that is used medically to reduce the severity of overdose in hospitals and the reduction of the withdrawal effects on the recovering addicts (Fudala et al, 1990). This reveals an aspect of this substance that was unknown previously. Buprenorphine is actually a narcotic that can be used as a substitute for the general opiate drugs that have associated with addictive effects and greatly severe withdrawal effects on stopping the use.
The fact that Buprenorphine comes with more manageable and mild effects makes it more suitable as a medical narcotic. It is being used today by both opioid-dependent men and women (who are not pregnant). Even more desirable in its properties is lack of the requirement to take it every single day and the presence of a combination with naloxone that can considerably reduce the addictive effects brought about by the normal opiate drugs that have been responsible for mortality and morbidity in the world following repeat use and ready availability (Fudala et al, 1990).
Mechanism of Buprenorphine.
The effect of Buprenorphine to the human brain is similar to the effect brought about by Opioids to the brain. This substance especially works more effectively when it interacts with the mu-receptor which is one of the opioid receptors. It is Therefore, it's mild effects that making a suitable candidate as compared to the traditional opiates that use the same pathways. This can be attributed to different notable properties of Buprenorphine.
First, it is a partial agonist. This means that it only partially acts as a treatment for opiate drug dependence (Jones, 20004). Acting on the same opioid receptors, this substance acts on the receptors producing the same effects but with moderate or reduced intensity when compared with the stronger opiates that act on the receptors fully to produce very strong effects that will have debilitating effects such as suppressed ability of the body to produce endogenous opiates. This is beneficial in that while it will lead to the pain alleviation, euphoria and the other associated side effects, they will be on a less severe scale (Whelan and Remski, 2012). This can help those of great drug dependence to satisfy their cravings using this drug while giving leeway for the body to slowly build its intrinsic functioning of producing endogenous opiates since Buprenorphine has the effect of reducing the strength of opiate drugs and thus tolerance of the body with time.
The second characteristic is in the high affinity it has for the mu-receptor. This characteristic is arguably the most powerful and explains its use in managing overdose. When Buprenorphine is administered, it binds tightly to the mu-receptor preventing other opiate drugs from getting to the receptors (Jones, 2004). This means that if a more lethal opiate drug is administered after Buprenorphine then it will be blocked from getting to the receptors. Alternatively, administration of Buprenorphine after overdose or use of another drug will lead to it displacing the other opiates from the mu-receptors. In the case of an overdose, this substance can be used to mitigate the potentially dangerous effects that van be brought about by an overdose even bordering on death.
The third desirable characteristic of this substance is the slow dissociation from the mu-receptor. This explains the fact that it stays longer and doesn't have to be administered daily for the effects to be seen (Jones, 2004). These three characteristics of Buprenorphine make up its three-pronged effective action in the brain and the body that aids in its working as a treatment for drug addiction and especially a highly recommended remedy for opiate-related complications brought about by prolonged use or involuntary overdose during medication in the hospital. There is another antagonistic property attributed to Buprenorphine that occurs on a second receptor, the kappa-receptor. Buprenorphine has been found to suppress the functioning of this receptor preventing its stimulation. As one of the three receptors that are stimulated by Opioids, the kappa receptor contributes immensely to the major symptoms associated with withdrawal after prolonged use such as chronic depression. The slowing of the activity of the kappa receptor is directly linked with increasing positive moods during rehabilitation since it slows down and mitigates depression at this time of the patient's recovery.
The research for opioid addiction treatment has been successful to some extent but there is still need for more research to develop and get better information on the available treatments. Ibogaine has regenerative properties, Ayahuasca is also a crucial substance for neuro-reconstruction while Buprenorphine has been identified as having great active presence in the regulation of the adverse effects brought about by opioid medication. The varying modes of action of these treatments contribute to the recovery of the autonomic opioid production system in the body presenting great milestones in the curbing of the opioid epidemic that has rocked the United States and continues to spread the world over. There still exist certain gaps in knowledge especially regarding the side effects associated with these treatments. Ibogaine was banned in the U.S because of certain undesirable effects that comes with prolonged use. These treatments however can, with advanced technology be formulated and combined with other substances to produce greater effect in their function. An example of where this has worked with stellar results is the combination of Buprenorphine and Naloxone which is currently one of the growing treatments of opiate addiction or overdose in the world.
The epidemic of death and suffering that has been brought about by increased opioid use over the years led to calls for mitigation measures to be put in place. The research activities have dug deep in a bid to find out the pattern of action of opiate drugs with the goal of identifying possible remedies. Buprenorphine, Ibogaine, and Ayahuasca are some of the treatment methods that have grown in popularity in recent years as great medications for opioid drug addictions and possible solutions drug overdoses associated with opioid drugs. However, these remedies have still presented the challenge of insufficient research especially in treatments like Ibogaine which if properly researched can be formulated to effectively decrease death due to drug overdose and rampant drug addictions that have afflicted the society for many years now.
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