was firm Share 60 +1 1 Pin 6 Stumble Reddit Shares 67 Phentermine is a sympathomimetic amine [derived from amphetamine] initially approved by the FDA in 1959 for the treatment of obesity. Its usage in the treatment of obesity was considered ideal due to the fact that phentermine suppressed appetite through central modulation of norepinephrine, and peripherally mobilized fat stores through catecholaminergic upregulation. That said, in the late 1990s phentermine was discontinued from pharmaceutical sale primarily based on findings that Fen-Phen (a combination drug of Fenfluramine plus Phentermine) damaged heart valves, increasing risk of serious cardiac events. When administered as a standalone agent without the presence of another stimulant, phentermine is considered reasonably safe. For this reason, it was reintroduced to the pharmaceutical market under the brand names Adipex-P, Ionamin, as well as generic phentermine. The drug remains commonly used for the short-term treatment of obesity, but some speculate that it could serve as a useful intervention for neuropsychiatric conditions, including major depressive disorder (MDD). Administration of phentermine is hypothesized to combat low arousal and fatigue commonly implicated in depression. Phentermine may alleviate depressive symptoms by increasing concentrations of norepinephrine and dopamine similar to that of Bupropion (Wellbutrin), an already approved antidepressant. Since around 1 in 3 patients with major depression fail to derive sufficient symptomatic relief from conventional pharmacology, phentermine may warrant investigation as an antidepressant. How Phentermine May Treat Depression (Mechanisms) There are numerous ways by which phentermine may prove helpful for individuals with depression. Phentermine functions as a TAAR1 agonist, meaning that it binds to, and stimulates TAAR1 sites. The stimulation of TAAR1 sites by phentermine generates an intrasynaptic release of monoamines including: norepinephrine, dopamine, and serotonin. Since monoaminergic activity is hypothesized as dysfunctional among a subset of those with depression, phentermine may ameliorate some of this dysfunction and enhance mood. Another possible means by which phentermine may improve mood is through its action upon VMAT2, resulting in bolstered monoaminergic release and signaling. It is also reasonable to consider that individuals with depression may benefit from phentermine s strong peripheral sympathomimetic effect. The potent effect of phentermine on the peripheral nervous system is understood to: enhance energy (for exercise), burn body fat (for weight loss), and augment centrally-mediated appetite suppression. A person with depression may find that increased energy leads to more exercise, weight loss improves self-esteem, and appetite suppression leads to caloric restriction [and modulation of neurotrophic factors] each of which may have a positive effect upon mood. Moreover, it is possible that a unique combination of phentermine s central and peripheral effects act synergistically to attenuate depression. Arousal increase : Administration of phentermine may be beneficial to those with depression due to the fact that it increases neurophysiological arousal. In a subset of individuals with major depression, abnormally low neurophysiological arousal may be a contributing or causative factor. Low neurophysiological arousal could be a result of numerous factors including: toxic exposures, illicit drug discontinuation, genetics/epigenetics, nutritional deficiencies, and more. Since the underlying cause(s) of abnormally low arousal cannot always be pinpointed and corrected, it is often helpful for depressed patients to increase neurophysiological arousal with pharmacology such as phentermine. Pharmacological increases in neurophysiological arousal often attenuate unwanted depressive symptoms such as psychomotor slowing and lethargy. Phentermine upregulates peripheral arousal by upregulating catecholamine concentrations such as those of: norepinephrine, epinephrine, and dopamine. The peripheral arousal should give individuals more energy to get out of bed and remain physically active. Though the central effect of phentermine may be less significant than its peripheral effect, it is known to also increase catecholaminergic signaling in the CNS. This could reduce symptoms such as brain fog and cognitive dysfunction, making it easier for someone with depression to think clearly. Brain wave modulation : Analysis of QEEG patterns among healthy individuals and those with certain types of depression reveals differences in neuroelectrical activity. Those with certain types of depression exhibit excessive amounts of slow-wave activity (e.g. theta waves) and insufficient amounts of fast-wave activity (e.g. beta waves) during waking consciousness. It is the phentermine-induced modulation of neuroelectrical activity that may facilitate a therapeutic effect among those with depression. While exact data regarding how phentermine affects neuroelectrical activity isn t available, it is thought to alter brain waves similar to that of its parent drug (amphetamine) and other psychostimulants such as methylphenidate. A study by Bresnahan et al. (2006) conducted on adults with ADHD discovered that dextroamphetamine (the dextrorotary isomer of phentermine s parent drug, amphetamine) suppressed slow wave activity, resulting in upregulation of fast waves. Though it is unclear as to whether similar effects would be observed in a population of individuals with depression, it is known that ADHD is a common comorbidity among those with depressive disorders. Furthermore, the neuroelectrical patterns of those with depression often exhibit overlapping commonalities to individuals diagnosed with ADHD. Perhaps a phentermine-induced upregulation in beta waves and coinciding downregulation of theta waves may be highly therapeutic for a subset of depressive patients. Source: http://www.ncbi.nlm.nih.gov/pubmed/16343642 Catecholamine release : Although at high doses phentermine is capable of modulating serotonergic signaling, a majority of its therapeutic antidepressant effect results from its ability to facilitate catecholamine release peripherally and centrally. In a subset of individuals with depression, suboptimal catecholaminergic signaling may be the chief neurobiological culprit. Specifically, those with depression could exhibit low norepinephrine , low dopamine , and possibly even abnormal epinephrine levels and/or signaling. Among individuals, treatment with a serotonergic modulator may prove ineffective, whereas treatment with phentermine may yield therapeutic benefit due its enhancement of catecholaminergic signaling. Deficient signaling from norepinephrine and dopamine are associated with: attentional deficits, cognitive impairment, fatigue, poor motivation, and weight gain each of which are common symptoms of depression. Administration of phentermine may reverse catecholaminergic dysfunction and improve mood. In addition, phentermine may improve a person s outlook and/or quality of life by enhancing attention, cognitive function, energy levels, and motivation. Users of phentermine may feel more alert and as though all previous mental fogginess associated with major depression has lifted. Though not everyone with depression derives benefit from upregulation of catecholamines, it is likely that some patients will. Dietary intake : Another interesting mechanism by which phentermine may improve mood is through its indirect effect on dietary intake. Phentermine is understood to function as an effective appetite suppressant, making it useful for weight reduction among those with obesity. It is theorized to suppress appetite by stimulating the release of norepinephrine from neurons within the hypothalamus. As a result, those taking phentermine find it easy to resist the temptation to consume excessive amounts of food. It is possible that ongoing treatment with phentermine leads to: caloric restriction, decreased intake of anti-nutrients (e.g. sugar), and increased intake of nutrient-dense foods. Ongoing caloric restriction is known to alter the brain by increasing concentrations of antioxidants, neurotrophic factors (e.g. BDNF ), and enhancing neurogenesis (growth of new brain cells) possibly enhancing mood. Decreased intake of anti-nutrients may reverse dietary-induced neurobiological underpinnings of depression. Finally, it may be easier to increase consumption of nutrient-dense foods while taking phentermine as a result of feeling consciously in control over hunger. Should a person increase consumption of nutrient-dense foods during treatment, this may mitigate preexisting micronutrient deficiencies that were causing depression. (For more information read: Best Diet for Depression ). Hormonal modulation : Another possible mechanism by which phentermine may be useful in the treatment of depression is via hormonal modulation. Individuals with depression often exhibit abnormalities in concentrations of hormones including: thyroid, epinephrine, and cortisol to name a few. Subtypes of depression characterized by abnormally low levels of neurophysiological arousal may benefit from increasing the aforestated stimulatory hormones with phentermine. A study by Hage and Azar (2012) specifically investigated thyroid levels among those with depression and discovered commonalities including: elevated T4, low T3, elevated reverse T3, and poor reactivity to thyroid stimulating hormone (TSH). Evidence suggests that phentermine may elevate T4 which could potentially worsen depression in a subset of individuals. That said, increasing T4 may improve mood among those with low T4 and/or hypothyroidism causing their depression. Deficiencies in peripheral levels of epinephrine and norepinephrine could also contribute to depression, provoking symptoms such as chronic fatigue and drowsiness. Phentermine is understood to increase concentrations of peripheral epinephrine (adrenaline) and norepinephrine (noradrenaline), likely increasing energy level and combatting depression-induced lethargy. It is also reasonable to hypothesize that phentermine may alter cortisol levels to improve mood. Since phentermine is a sympathomimetic agent, it should be suspected that it would increase secretion of cortisol and/or prolong its degradation. Although 50% of individuals with major depression secrete excessive amounts of cortisol (making phentermine a poor choice of treatment), others may secrete insufficient amounts of cortisol. Research by Maripuu et al. (2014) documents that individuals with low cortisol secretion experience depression and poorer mood than those with optimized levels of cortisol. Assuming someone with low cortisol secretion administers phentermine for depression, it is possible that increasing his/her cortisol levels within a healthier range may improve mood. Though phentermine may not correct the underlying root cause of the low cortisol (e.g. HPA axis dysfunction), the increase in cortisol may ameliorate depressive symptoms resulting from suboptimal cortisol production such as cognitive deficits and tiredness. If phentermine is capable of modulating cortisol, this modulation could indirectly impact CNS function. The relationship between the peripheral nervous system and central nervous system is bidirectional, meaning that altering activity in the PNS should affect activity within the CNS; and vice-versa. Upon modulation of peripheral hormones, signal transmission from the peripheral nervous system to the central nervous system is altered resulting in neurobiological changes. Although phentermine exerts a strong peripheral effect, it would be myopic to assume that its peripheral effect wouldn t indirectly alter brain activity to improve mood. Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3246784/ Source: http://www.ncbi.nlm.nih.gov/pubmed/24932586 Neural activation : Though detailed neuroimaging studies assessing the effects of phentermine upon brain function haven t been conducted, it is thought that phentermine affects activity in multiple regions of the brain. Alterations in neural activation such as by increasing activity in certain regions and/or decreasing activity in other regions may yield therapeutic effects for those with depression. Some areas of the brain that may be affected by phentermine administration include the: prefrontal cortex, HPA axis, and nucleus accumbens. A subset of individuals with depression exhibit hypofrontality or deficient function of the frontal lobes and prefrontal cortex. Hypofrontality results in impaired executive abilities such as: abstract thinking, attention, complex analysis, emotional regulation, and organization of thoughts. With a suboptimally functioning prefrontal cortex, it s difficult to think logically about feasible ways to treat and/or cope with depression. Administration of phentermine may enhance noradrenergic and dopaminergic signaling within the CNS, which could ameliorate hypofrontality. Reversal of hypofrontality should improve cognitive function, increase ability to cope with a depressed emotional state, as well as dilute the severity of depression. Another region of the brain that s affected by phentermine is the hypothalamus. The effect of phentermine upon the hypothalamus is associated with improved appetite regulation, but may also improve mood. A myriad of studies have discovered HPA (hypothalamic-pituitary-adrenal) axis dysfunction to be implicated in major depression. Since phentermine modulates hypothalamus activity, it is possible that it ameliorates HPA dysfunction and promotes normalization of mood. Arguably the most significant means by which phentermine-induced neural modulation improves depressive symptoms is by targeting the nucleus accumbens. The nucleus accumbens is a region of the brain responsible for mediation of motivation and reward. Dysfunction within this particular region may be dictate the severity of depressive symptoms such as motivation, cognitive impairment, and lethargy. A study by Hong et al. (2016) reported that phentermine administration activates the PI3K/Akt pathway within the nucleus accumbens of mice, motivating them to attain rewards. Though these findings haven t been replicated in humans, it is reasonable to hypothesize that similar modulation of activity within the nucleus accumbens occurs. Research by Bewernick et al. (2012) discovered that deep brain stimulation targeting the nucleus accumbens of individuals with depression is a highly effective treatment with a sustained antidepressant effect. Assuming phentermine is able to activate pathways within the nucleus accumbens of humans, mood may be enhanced. It should also be considered that simultaneous modulation of activity within the prefrontal cortex, hypothalamus and/or HPA axis, as well as the nucleus accumbens generates an antidepressant response. Source: http://www.ncbi.nlm.nih.gov/pubmed/26887589 Source: http://www.ncbi.nlm.nih.gov/pubmed/22473055 Source: http://www.ncbi.nlm.nih.gov/pubmed/15014598 Physical exercise : A significant problem among those with major depression is that they find it difficult to engage in physical activity as a result of fatigue, motivational deficits, and sleepiness. Remaining sedentary due to low energy associated with depression may exacerbate depression and create a vicious circle of reinforcement in which: the depression promotes inactivity AND inactivity promotes depression. Breaking the vicious circle by forcing oneself to exercise frequently may be what s necessary to attenuate depression. Phentermine may help an individual with depression by increasing energy levels and motivation, making it easier to engage in physical activity. Assuming phentermine enables a person with depression to exercise regularly, this will: alter brain activity, neurotransmitters, hormones, and even neurotrophic factors. For example, it is known that aerobic exercise increases BNDF levels and promotes hippocampal neurogenesis each of which are associated with mood enhancement. Other psychological benefits of exercise include: boosted confidence and self-esteem. A person s appearance and physical health may also improve as a result of weight loss from physical activity which could also decrease depression. Moreover, the instillation and adherence to an exercise habit may be associated with positive momentum ultimately reducing depression. Weight loss : There s often an association between depression and obesity, as well as being overweight. A systematic review and meta-analysis by Luppino et al. (2010) reported a reciprocal link between depression and obesity. It may be subject to individual variation in regards to whether: depression causes obesity, obesity causes depression, or both conditions emerge simultaneously. Nevertheless, depression makes it difficult to resist unhealthy foods and being overweight makes it difficult to avoid feeling depressed. One reason those with obesity may struggle with depression is a result of poor self-image, as well as inability to find a suitable mate. Another is that obesity alters gut bacteria, hormone production, and neurotransmitter levels in the brain all of which likely reinforce depression. Phentermine is understood to be an efficacious agent for weight loss. It helps individuals lose weight by decreasing appetite and burning excess body fat. Assuming someone ends up losing a significant amount of weight during treatment, it is likely that this weight loss may reverse depressive symptoms. Weight loss may shift gut bacteria, alter hormone production (e.g. testosterone), and neurotransmitter production to boost mood. Losing weight may also help an individual attract a mate and/or social relationships as a result of improved appearance resulting in an antidepressant effect. Moreover, weight loss usually improves self-esteem and confidence, each of which may be useful in attenuation of depression. Source: http://www.ncbi.nlm.nih.gov/pubmed/20194822 Benefits of Phentermine for Depression (Possibilities) Phentermine hasn t been investigated for the treatment of depression, but there may be some benefits to be attained from its usage even if the usage is only short-term. The most substantial benefit associated with using phentermine for depression is that it functions atypically compared to conventional antidepressants and is faster-acting. Furthermore, it may be more effective than serotonergic agents for enhancing motivation and cognitive function. Other benefits of using phentermine include: its side effect profile (compared to SSRIs ) and its ability to promote weight loss. Atypical intervention : When treating major depression, not everyone responds to medications that target the serotonin system. Individuals diagnosed with atypical depression in which serotonergic dysfunction isn t implicated may benefit more from unconventional pharmacology. Phentermine may serve as a unique intervention in that it chiefly releases norepinephrine, modestly releases dopamine, and negligibly releases serotonin. This unique central mechanism, as well as a strong peripheral catecholaminergic effect, may alleviate depressive symptoms among non-responders to conventional psychopharmacology. Cognitive enhancement : A debilitating symptom often associated with major depression is cognitive impairment. Those experiencing cognitive impairment as a result of depression often have a difficult time with cognitively-demanding occupational and/or academic tasks. Difficulty with cognitively-demanding tasks may lead to increased stress and exacerbate underlying low mood as a result of ineffectiveness. Phentermine may ameliorate cognitive dysfunction by upregulating catecholamine signaling, possibly also reversing hypofrontality (as is seen in some cases of depression). If phentermine enhances cognitive function to reverse deficits, this may increase confidence, competence, and ultimately mood. Energy increase : Those that take phentermine at clinically relevant doses for weight loss generally report a significant increase in energy. This energy increase results from activation of the sympathetic nervous system and release of catecholamines. Individuals with depression that are struggling with symptoms such as: drowsiness, fatigue or lethargy, and/or tiredness may find that phentermine gives them enough energy to be productive and accomplish tasks at home, school, and work. Efficacy : The efficacy of phentermine as an intervention for depression is unknown. However, there are anecdotal reports circulating from a subset of users suggesting that phentermine transformed their personality and enhanced their mood. These anecdotal reports indicate that phentermine may be an effective antidepressant among a subset of those who use it. Fast-acting : In many cases, it takes between 4 and 8 weeks for the therapeutic effects of an antidepressant to emerge. A major problem with antidepressants taking so long to work is that a person with depression may be unable to wait the person may need immediate benefit in order to function and avert his/her suicidal ideation. An advantage of using a drug like phentermine that triggers release of catecholamines (norepinephrine and dopamine) is it s fast acting mood enhancement. Some users may experience noticeable mood improvement on their first day of treatment, providing nearly instantaneous symptomatic relief. Habit instillation : During treatment with phentermine many patients introduce new lifestyle habits in effort to lose weight. Phentermine is known to improve physical stamina and self-control associated with food intake. This may lead patients to engage in regular exercise, reduce caloric intake, and modify their diets (e.g. eliminate unhealthy foods and increase nutrient-dense foods). Instilling the habits of exercise, caloric restriction, and consumption of nutrient-dense diets may improve overall health while simultaneously improving mood. Motivation increase : Anecdotal reports from humans suggest that phentermine is capable of increasing motivation. Studies of phentermine administration in mice discovered that the drug activates a specific pathway in the nucleus accumbens of the brain, resulting in increased motivation to attain reward. Many serotonergic antidepressants have no significant effect upon motivation and/or may uplift mood while simultaneously decreasing motivation. The motivation increase derived from phentermine may help with productivity and reverse underlying reward deficiencies . Side effects : The side effect profile of phentermine may be preferred to the side effect profile of conventional antidepressants. Unlike standard antidepressants, phentermine isn t associated with weight gain or sexual dysfunction. A reason numerous people complain about SSRIs and/or end up discontinuing treatment has to do with the fact that they gain a lot of weight or are no longer interested in sex. Those taking phentermine are more likely to gain weight and experience heightened libido making it preferable for some patients. Weight loss : It is well known that phentermine is FDA approved for the short-term treatment of obesity by promoting weight loss. Research suggests that many individuals with depression also suffer from obesity and/or are overweight. Since phentermine helps with weight loss, and may also improve mood it could be used to treat both conditions simultaneously. Additionally, weight loss may be a direct mechanism by which the drug improves mood. Someone who is overweight may feel worse about their body image and/or stressed about other obesity-related health conditions (e.g. diabetes). Losing weight should improve self-esteem, decrease stress associated with obesity-related health conditions, and may also help a person attract a mate all of which may have positive implications for those with depression. Drawbacks of Phentermine for Depression (Possibilities) Despite the possible benefits to be attained from utilizing phentermine as an antidepressant, significant potential drawbacks should be discussed. Arguably the biggest drawback associated with phentermine usage for depression is that it may exacerbate the severity of depressive symptoms in certain users and suicidal ideation. Additionally, even if phentermine proved effective for the short-term treatment of depression, its antidepressant effect is unlikely sustainable over the long-term. Moreover, long-term administration of phentermine may lead to serious medical conditions such as heart valve damage, pulmonary hypertension, or stroke. Abuse & addiction : Despite having a lower potential for abuse than amphetamine isomers, phentermine is classified as a Schedule IV substance indicating that it still could be abused. Studies have shown that high doses of phentermine cause feelings of euphoria, likely as a result of its simultaneous release of central norepinephrine and dopamine. Assuming someone begins abusing phentermine, it is possible that this abuse may lead to development of a phentermine addiction. Both abuse and addiction are problematic in that they increase risk of serious adverse effects especially following tolerance onset. Contraindications : Phentermine is contraindicated for usage among those with: a history of drug abuse or dependence, diabetes, neuropsychiatric disorders, hyperthyroidism, glaucoma, kidney disease, cardiovascular disease, and hypertension. Taking phentermine with one of the aforestated medical conditions may provoke adverse effects and/or lead to fatality. For example, someone taking phentermine with cardiovascular disease could experience a heart attack resulting from excessive vasoconstriction and hypertension. These contraindications my limit the number of individuals that could safely take phentermine for depression. Controlled substance : It is understood that phentermine is classified as a Schedule IV controlled substance. While this scheduling indicates that phentermine may be less habit forming and/or risky than substances in other schedules, it suggests that it may result in abuse and/or dependence. In addition to the possibility of abuse and/or dependence, the scheduling of phentermine as a controlled substance makes it more difficult for users to attain a prescription. Even if you were able to attain a prescription, some doctors may require frequent visits for a phentermine refill. Frequent visits are required to ensure patient safety and rule out possibility of abuse. Dependence : Taking phentermine for depression may work well initially, but should an individual attempt to discontinue treatment, he/she may realize that it is impossible to function without the drug. A person may become reliant upon phentermine in order to socialize with others, perform at work and/or school, as well as for well-being. While some may argue that dependence is fine as long as depression is treated, the dependence may be problematic in that it may lead to high-dose/long-term treatment resulting in deleterious long-term effects. Depression increase : There s no research to suggest that phentermine is likely to reduce depression, but there is some evidence noting that phentermine can worsen depression. Many individuals with depression exhibit already-high concentrations of norepinephrine, epinephrine, T4, and cortisol. Phentermine ingestion may further increase the problematic neurobiological underpinnings of certain depressive subtypes, leading to exacerbation of depression and possibly suicidal ideation. Since phentermine may significantly increase depression in some users, and isn t a proven intervention, it may be worth avoiding. Interactions : Phentermine is contraindicated for usage with other antidepressants, as well as sympathomimetic agents due to interactions. Administering phentermine along with antidepressants such as SSRIs, SNRIs , TCAs , and MAOIs may cause serotonin syndrome or abnormally high serotonin within the CNS. Medical professionals also recommend avoiding usage of phentermine with alcohol, drugs that increase blood pressure, psychostimulants, and many other agents that modulate central and/or peripheral nervous system function. Furthermore, it is possible that phentermine may decrease the efficacy of various medications due to pharmacokinetic interactions (e.g. inhibition of absorption). As a result of the myriad of possible phentermine interactions, it fairly impracticable as an adjunct. Long-term effects : The long-term effects of phentermine could be downright dangerous for some users, especially those that use the drug at high doses. The cumulative effect of phentermine administration over an extended duration may lead to heart valve damage, pulmonary hypertension, cardiac events, and/or transient ischemic attacks. For this reason, the drug is generally reserved solely for short-term administration. Since individuals with depression often require long-term treatment (exceeding 3 months) and will likely want to avoid long-term effects phentermine is a poor treatment choice. Non-evidence based : Among the most substantial drawbacks associated with using phentermine for depression is that it s non-evidence based. In other words, there s zero scientific evidence to support the usage of phentermine as an antidepressant. For this reason, it is unlikely that any medical professional would prescribe phentermine, even as an off-label intervention to an individual struggling with depression. There are a multitude of other antidepressants that have undergone rigorous scientific testing (in RCTs) and are considered safe and effective. There hasn t even been so much as a proof of concept trial of phentermine for depression in humans. Short-term only : It is widely known that phentermine is approved by the FDA for the treatment of obesity. However, it is intended to be used for a duration of less than 3 months. Anyone using phentermine for a duration exceeding a 3-month term may increase likelihood of serious adverse reactions such as heart valve dysfunction and cardiac complications. Subjecting a person s body to ongoing vasoconstriction and enhanced sympathetic tone for months, without taking a break, may take a cumulative toll on organ function and other endogenous processes. Moreover, it is highly likely that users could become tolerant to high doses of phentermine if used in excess of 3 months, and upon onset of tolerance, its therapeutic antidepressant effect subsides. Side effects : Various phentermine side effects that you may experience during treatment include: anxiety, dizziness, hair loss, headache, insomnia, nausea, and vomiting. Many of these side effects are problematic in that they may indirectly worsen depressive states and/or neuropsychiatric comorbidities. For example, if phentermine were to cause anxiety and insomnia as side effects this combination of feeling tense and being unable to get proper sleep may exacerbate your depression. Moreover, side effects such as dizziness, nausea, and vomiting may impair your ability to function leaving you with no option but to discontinue phentermine. Superior options : While phentermine exhibits a unique mechanism of action, it acts primarily upon the peripheral nervous system and less significantly upon the central nervous system. The reduced effect exerted upon the CNS may make it a poor fit for the treatment of depression and neuropsychiatric conditions. What s more, even if phentermine turned out to be safe and efficacious as an antidepressant, it may be significantly less safe and effective when compared to already-approved antidepressants. In other words, there may be plenty of superior psychopharmacological treatment options. Moreover, those in search of non-serotonergic interventions have plenty of choices including Bupropion (Wellbutrin) which is FDA approved as an antidepressant and has been compared to phentermine as a result of its mechanism. Tolerance : Those that take phentermine for long enough are bound to develop some sort of tolerance to its effect. Tolerance occurs due to the fact that neurochemistry and physiology of the users adapts to the effects of the drug and adjusts itself accordingly. Regular phentermine-induced release of norepinephrine and dopamine will essentially train the brain to downregulate its endogenous production of each neurotransmitter, as well as decrease receptor sites due to saturation. As a result of these changes, those that experience a m no use
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