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What Does THC Do To The Brain And The Body?

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What Does THC Do To The Brain And The Body
December 31, 2019
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THC is responsible for producing the coveted “high” associated with cannabis use. Aside from this, it also has a healing effect on both the brain and the body. That makes it a valuable therapeutic agent for a variety of ailments and symptoms. However, when consumed irresponsibly or excessively, it may cause adverse reactions both in the short- and long-term instead.

Understanding THC

Tetrahydrocannabinol (THC), found mostly in the resin-filled trichomes, is one of the 113 currently identified cannabinoids. It is arguably the most well-known and most researched of all the cannabinoids. And, it is also the primary psychoactive ingredient of cannabis.

To exert a range of effects, THC interacts with the body’s endocannabinoid system (ECS), which comprises of cannabinoid receptors, endocannabinoids, and metabolic enzymes. It is a complex modulatory network that plays a key role in maintaining homeostasis – the stability of the internal body condition. Moreover, the ECS regulates a variety of physiological functions and processes, including:

  • Sleep
  • Mood and stress
  • Cognition, learning, and memory
  • Appetite
  • Metabolism
  • Pain
  • Immune response
  • Bone development, remodeling, and growth
  • Muscle formation
  • Movement
  • Central nervous system (CNS) function
  • Cardiovascular system function
  • Liver function
  • Reproductive system function
  • Skin function

The effects of THC vary from person to person and depends on a variety of factors, including the strain, quality of the product, potency, dose, administration method, body chemistry, tolerance level, and metabolism, among others.

How It Affects The Brain

THC affects the brain by mimicking the naturally occurring endocannabinoids – also referred to as the endogenous cannabinoids. It also interacts with the receptors of the ECS – CB1 found in the CNS and CB2 in the peripheral nervous system. THC more readily binds with the CB1 receptor, mainly because it shares a similar structure with anandamide (AEA).

Also known as the “bliss molecule,” AEA has a high affinity with the CB1 receptor and modulates brain function, flooding the brain with dopamine. This neurotransmitter plays a role in pleasure, happiness, and a sense of well-being. It is through this process that cannabis can bring forth the coveted rush of euphoria.

Brain Effect Image

The moment THC activates the CB1 receptor, it also assumes the brain regulation task of AEA. However, THC does not necessarily affect the body the same way that AEA does.

First, AEA only releases small amounts of dopamine, whereas THC releases the neurotransmitter at much higher concentrations. Second, the metabolic enzymes in the ECS quickly break down AEA upon completing its task. Since such enzymes do not work on THC, the psychoactive compound lingers much longer in the body.

Ultimately, the barrage of chemical signals may disrupt brain activity and overwhelm the homeostatic action of the ECS. That is why THC can produce a satisfying high, but may also induce unwanted mental upshots when used in excess.

How It Affects The Body

THC demonstrates a physiological impact by affecting the brain.
Upon interacting with the ECS, THC influences the communication system in the brain. More specifically, it alters the release of the neurotransmitters. Also known as the body’s “chemical messengers,” these neurotransmitters relay signals and information between cells. It is also involved in pain detection, immune function, mood, and sleep, among others.

In essence, THC can regulate and shape how the cells send, receive, and process information.

Body of a woman

Moreover, the effects of THC on the body depend on which brain area is involved. For instance, affecting the limbic system may modify memory, emotional response, cognition, and motor movement, among others. Meanwhile, the mesolimbic pathway is responsible for the reward, motivation, pleasure processes, and more.

Health Benefits

Due to the effects of THC on the ECS – and, ultimately, the brain and the body – it could bring about an array of benefits useful for treating different conditions.

Antidepressant

A 2005 study published in the European Neuropsychopharmacology investigated the role of the CB1 receptor in inducing antidepressant-like effects. The results revealed that lab mice had reduced immobility by as much as 50 percent after being subjected to the rat Porsolt forced swim test (FST). This effect on movement is similar to the one induced by conventional antidepressants. It suggests that the CB1 receptor could be the target of future antidepressant drugs.

Given the putative role of the ECS in mood regulation, as well as the euphoric effects of THC, it is unsurprising that more people seeking relief from depression are turning to cannabis. Thus, in a 2006 study published in the Addictive Behaviors, the link between cannabis use and depressive symptoms was assessed in an internet survey.

For respondents, researchers gathered more than 4,000 profoundly depressed and active users. According to the data collected, those who used cannabis at least once a week experienced reduced depression, a more positive mindset, and fewer bodily discomforts. The results are promising as it shows that the plant could be used to address the illness without worsening any preexisting depressive symptoms.

In 2010, a study aimed to investigate the antidepressant activity of THC and other cannabinoids using the automated mouse FST and tail suspension test (TST). The results showed that only 2.5 mg/kg of THC was enough to exert significant antidepressant action in the FST and TST. These findings, published in the Pharmacology Biochemistry and Behavior, suggest that the antidepressant-like effects of THC could contribute to the overall mood-elevating properties of the compound.

While THC offers immediate, short-term relief by enhancing mood, it may also have substantial effects in the long run. Since chronic administration of antidepressants may lead to adult hippocampal neurogenesis, it is not farfetched that THC will do the same. That is the basis of a 2013 review published in the Current Neuropharmacology, exploring the interplay between THC, CB1 and CB2 receptors, and proliferation and neurogenesis in the hippocampus.

After analyzing more than 20 in vitro and in vivo studies, researchers found that stimulating the cannabinoid receptors may regulate hippocampal neurogenesis. It substantiates the findings of an earlier study published in the Journal of Clinical Investigation, reporting that long-term cannabis use may promote adult hippocampal neurogenesis.

Treatment For Sleep Disturbances

Sleep-related apnea, characterized by the involuntary cessation of breathing for short periods, is a potentially life-threatening sleep disorder. The neurotransmitter is known for exacerbating this condition. Thus, a 2002 study published in Sleep investigated the effects of blocking serotonin activity on sleep-related apnea. Researchers used cannabimimetic agents oleamide and THC, both of which are serotonin antagonists. The results revealed that the intraperitoneal injection of THC in rats improved respiratory stability during sleep. This action could be tapped for the future development of medications for the treatment of sleep-related breathing disorders.

The potential as a treatment are substantiated in a more recent 2013 single-center, dose-escalation trial published in the Frontiers in Psychiatry. In this study, 2.5-10 mg of dronabinol – a synthetic THC – was administered daily for three weeks in patients with obstructive sleep apnea (OSA). Since it neither induced adverse effects nor interfered with sleep, it was found to be a safe, effective, and well-tolerated treatment for OSA.

Aside from helping with sleep apnea, a 2004 study demonstrated that THC might also be useful for insomnia. The double-blind placebo-study, published in the Journal of Clinical Psychopharmacology, examined the effects of THC and other cannabinoids on nocturnal sleep, early-morning performance, sleepiness, and memory in 8 healthy young adults. The data revealed that an oromucosal spray consisting of 15 mg of THC increased sleepiness and produced sedative effects, but may impair memory and had no significant effects on nocturnal sleep.

Analgesic

Antinociception is most likely the cause of the analgesic properties of THC. In 2001, a review published in the Progress in Neurobiology highlighted how CB1 and CB2 receptor agonists like THC produced antinociception in animal models, and, in turn, how the cannabinoid-induced antinociception could help central and peripheral pain. The significance of this study is that it brings to light the connection between the CB1 and CB2 receptors and pain modulation.

In another study, researchers found that intrathecal injection WIN 55,212-2 – a cannabinoid receptor agonist like THC – generated hyperalgesia by acting on the spinal and peripheral sites. The results, published in Pain: The Journal of the International Association for the Study of Pain in 2001, also indicated that the antihyperalgesic properties only appear to be present at doses that do not produce antinociception. Still, it substantiated the role of cannabinoid receptors in pain response and regulation.

Since THC binds with both the CB1 and CB2 receptors, these results opened up the therapeutic value of the compound in managing different types of pain, including chronic, debilitating ones. It is a monumental discovery, as the most commonly prescribed medication for constant, severe pain are opioid analgesics. This class of drugs attaches to the opioid receptors in the body. Although it works, opioids are rife with side effects and can be highly addictive.

The need for a safer and more tolerable pain reliever became the motivation behind a 2009 review published in the Journal of Opioid Management. Researchers surveyed clinical and experimental studies that explored the potential of the cannabinoids in treating neuropathic pain, inflammatory pain, and cancer pain to assess how the analgesic ability of cannabis could be used to treat excruciating pain. The data revealed that aside from being a potent analgesic agent, THC also worked in synergy with opioids, as well as served as opioid-sparing agents to lessen severe pain.

Such a revelation has two significant implications. First, when THC is used as an adjunct to opioids, it means lower doses of opioids could already offer relief while having fewer side effects. Second, it corroborates the potential of the cannabinoids in countering pain.

To date, one of the latest scientific proof comes from the 2018 study filed in Frontiers in Pharmacology. After analyzing both preclinical and clinical research on the use of medical cannabis for pain, researchers concluded that there is high-quality evidence supporting the use of medical cannabis in treating chronic pain in adults. Still, larger, more extensive well-designed studies are required to assess the long-term efficacy and safety of the plant.

Anti-Inflammatory

In 2009, the seminal work on the anti-inflammatory properties of THC and other cannabinoids were published in the Future Medicinal Chemistry. The goal of this review was to understand the physiological mechanism of the compounds, the influence of the CB1 and CB2 receptors, and the role of the ECS as a whole.

Upon analyzing existing data, researchers found that THC suppressed inflammatory responses by promoting cell death, inhibiting cytokine and chemokine production, and upregulating the T-regulatory cells (Tregs). The CB1 and CB2 receptors play a crucial role in the modulation of the immune system. Meanwhile, the metabolic enzymes in the ECS also facilitated immunosuppression and swift recovery from injuries related to the immune system.

All these suggest that manipulating THC and other cannabinoids could be useful in formulating a potent agent against inflammatory and autoimmune diseases and symptoms.

Anti-Spasmodic

Stiff, sore, and cramping muscles or involuntary muscle contractions or spasms characterize muscle spasticity. These symptoms typically occur in patients with multiple sclerosis (MS), as well as those suffering from brain or spinal cord injuries.

In 2014, a systematic review published in the Neurology analyzed the scientific literature on medical cannabis from 1948 to 2013 – with an emphasis on its use as a treatment for the symptoms of MS, epilepsy, and movement disorders. THC was found to be effective at reducing patient-reported spasticity in individuals with MS, as well as treating painful spasms or MS-related pain.

A year later, another systematic review and meta-analysis published in The Journal of the American Medical Association validated previous findings. After examining a total of 79 trials on the medical use of the cannabinoids, researchers concluded that moderate-quality evidence supported the use of THC and other compounds in the treatment of spasticity and chronic pain. However, there are no significant findings regarding the use of THC in spasticity induced by spinal cord injury.

Helps With Low Appetite

Both anecdotal evidence and studies reveal that THC may stimulate the appetite and food intake – or more colloquially known as “the munchies.” This mechanism could be beneficial for patients suffering from anorexia and weight loss as side effects of various ailments.

In 2005, a study looked into the efficacy of cannabis in managing the symptoms of human immunodeficiency virus (HIV) infection, including poor appetite, nausea, muscle pain, nerve pain, paresthesia, anxiety, and depression. Researchers used a cross-sectional survey design and recruited more than 500 HIV-positive individuals. Of the 143 participants who used cannabis for symptom relief, 97 percent reported improved appetite. The results were published in the Journal of Pain and Symptom Management.

In 2006, another research investigated the effects of THC in appetite – this time in cancer-induced anorexia (CCA). The objective of this double-blind, randomized, placebo-controlled trial was to assess the efficacy of THC as an orexigenic agent in 80 advanced cancer patients with chemosensory abnormalities. The data revealed that THC induced premeal appetite and enhanced the flavor of foods by acting on the reward pathways in the brain. Do note, however, that the findings were not very different from the ones obtained in placebo.

Two notable studies explored the action behind the appetite stimulant abilities of the compound.

The first one, filed in the Proceedings of the National Academy of Sciences of the United States of America in 2011, found that endocannabinoids like AEA and 2-arachidonoylglycerol (2-AG) induced appetite by acting on the CB1 receptors. Conversely, inhibiting CB1 receptor activity may cause anorectic effects, which probably resulted in an antagonistic effect on appetite-related hormones such as leptin, ghrelin, and corticosterone.

While the action behind it is still not fully understood, the orexigenic function of the endocannabinoids and CB1 receptors cannot be repudiated. This agrees with the previous notion that the endocannabinoids and CB1 receptors could reinforce the gustatory and olfactory properties of food.

Since THC can interact with the CB1 receptor due to similarity with AEA, it is not unlikely to trigger appetite via the same mechanism. This is the foundation of the second study, which was published in the Brain Research in 2012. In the placebo-controlled trial involving HIV infected adult men, it was found that THC increased the plasma levels of the hormones ghrelin and leptin. The findings substantiate the presumed role of the cannabinoid receptors in the regulation of the appetite hormones.

Finally, aside from improving appetite, THC may also help avoid weight loss.

In a 2011 study published in the Neuropsychopharmacology involving rodent models of anorexia, researchers exploited the reward pathways in the ECS to manipulate food intake and, in turn, possibly reverse weight loss. The results showed that the subchronic administration of THC prevented significant body weight loss, as well as increased food intake for a brief period. It attests to the effectiveness of the ECS in reducing weight loss. More importantly, the findings could be tapped further for the treatment of AN in humans.

True enough, in 2014, a randomized control trial (RCT) assessed the effects of dronabinol treatment on body weight on 25 women with severe AN. After receiving 2.5 mg of synthetic THC twice a day for four weeks, the women experienced small but significant weight gain without any adverse effects. The results were published in the International Journal of Eating Disorders.

Anti-Nausea And Anti-Emetic

In many cases, treating chemotherapy-induced nausea and vomiting (CINV) is challenging. While there are currently available pharmacological options, many patients respond poorly to these medications. The need for a more effective anti-sickness drug became the basis of several studies on medicinal cannabis use.

As early as 1983, a study has already investigated the efficacy of THC and other cannabinoids as anti-nausea and antiemetic agents. These results, published in Drugs, found that nabilone – another type of synthetic THC – was more effective than prochlorperazine in preventing chemotherapy-induced vomiting.

Further validation of the antiemetic properties of THC came in a 2001 systematic review from The BMJ. Researchers analyzed 30 RCTs comparing the efficacy of cannabis with any other antiemetic drugs or placebo in chemotherapy. Oral nabilone and dronabinol and intramuscular levonantradol (an analog of dronabinol) were found to be more effective in inhibiting emesis than conventional medications like prochlorperazine, metoclopramide, and chlorpromazine, among others. The data demonstrated that THC could be a useful adjuvant for managing chemo-related ailments. However, the side effects of the compound, such as the psychoactive high, should be taken into account.

In 2017, the antiemetic abilities of the cannabinoids received another boost in a study published in Cancer Chemotherapy and Pharmacology. Aside from efficacy, the study also explored the pharmacokinetics (PK), pharmacodynamics (PD), and the safety of the compounds for patients suffering from CINV. After analyzing the literature, researchers concluded that oral THC and other cannabinoids exhibited a similar or improved efficacy compared with traditional drugs for CINV. Moreover, the newer formulations of oral THC offered superior PK/PD profile than previous versions.

Anti-Tumor And Anti-Proliferative

Cancer patients may benefit from the curative abilities of cannabis, as well as the regulatory role of the ECS in pain, inflammation, and energy metabolism, among others. As demonstrated earlier, it could address pain, lack of appetite, nausea, and vomiting. However, a wealth of scientific evidence also points to the anti-proliferative and anti-angiogenic effects of the cannabinoids both in vitro and in vivo in cancer models. This is what the 2014 study published in Oncotarget aimed to investigate.

After reviewing cell culture systems and complex animal models, the data revealed that THC and other chemical compounds exerted an anti-proliferative effect on tumors. It also modulated vital cell signaling pathways, which played a role in cell survival, proliferation, angiogenesis, and metastasis, among others.

In 2006, a study published in the Current Oncology examined the anticancer mechanisms of the cannabinoids in more detail. After analyzing the molecular mechanism of action using experimental models of cancer, the compounds were deemed to have an acceptable safety profile. More importantly, the researchers suggested that future clinical trials should explore its efficacy as a single drug or when used in combination therapies in different types of cancer.

Only recently, the potential of the cannabinoids received further validation in a 2019 study published in the Bosnian Journal of Basic Medical Sciences. Aside from verifying that THC and other compounds could regulate tumor growth, the findings also revealed that the antitumor effects might depend on the dose, concentration, and cancer type. The significance of the study is that it mentioned which research areas to tackle for the future development of therapeutic agents for cancer patients.

May Ease Glaucoma

Science reveals that THC may be a potential remedy for glaucoma, an eye condition that can damage the optic nerves. It is linked to increased intraocular pressure (IOP) – or the rise of fluid pressure within the eyes. This disease gets progressively worse over time and may result in irreversible blindness if left untreated. Often, doctors would prescribe eye drops, oral medications, laser treatment, surgery, or a combination of these options. Still, new and more superior treatments are warranted.

As early as the 1970s, evidence has already hinted at the potential of THC in remedying glaucoma. That is the motivation behind a 2004 study published in the British Journal of Pharmacology, which found that THC may effectively lower the fluid pressure inside the eyes.

In 2006, a review published in the Current Opinion in Ophthalmology affirmed the previous findings and added that the compound is an ocular hypotensive agent or a substance that reduces the blood flow in the eyes. That is because THC lowers the blood pressure (hence, the signifier “hypotensive”) once it enters the bloodstream, which then causes the IOP to drop as well. The study also noted that the compound might have unpleasant cardiovascular and neurological effects, which could also diminish the IOP lowering action of THC. At any rate, further research is required for the formulation of a safe, effective, and stable THC-based topical product.

Risks

Although full of medicinal benefits, THC may also generate unwanted psychological, cognitive, and physiological reactions. These typically manifest itself immediately, either after heavy use or after long-term consumption.

Risks Sign

Short-Term Side Effects

When used in excess, the pleasurable mind-altering effects may turn into an intense, possibly incapacitating high. Unpleasant mental and physical effects may also occur. To avoid any acute adverse effects, dose carefully and slowly, and remember to factor in the tolerance to THC.

Psychological/ Mental

  • Distorted senses and perception (sight, sounds, touch, time, time)
  • Difficulty learning or retaining information
  • Impaired short-term memory
  • Altered judgment
  • Paranoia (in high doses)
  • Psychosis-like symptoms (in high doses)

Physiological

  • Dry, bloodshot eyes
  • Cottonmouth
  • Extreme nausea and vomiting
  • Breathing difficulties
  • Rapid heart rate
  • Chest pain
  • Impaired motor skills and coordination
  • Increased risk of driving accidents and other injuries

Long-Term Side Effects

Science suggests that early, heavy, and chronic exposure to THC may produce detrimental effects. While further evidence is needed to verify these claims, it is still a cause for worry. More importantly, it stresses the urgency of practicing safe and responsible consumption.

Risk of Addiction. A 2007 study published in the Addiction Science and Clinical Practice brought to attention the increasing prevalence of marijuana abuse and dependence in both adults and adolescents – otherwise known as cannabis use disorder (CUD).

Of concern are young people who started smoking early, as early-onset drug use increases the risk for drug dependence problems later in life. These are the findings of a 2009 study published in the Addictive Behaviors.

Another research published in the Journal of Neuroimmune Pharmacology in 2018 assessed the addictive potential of cannabis using the Koob and Volkow model of addiction. It conformed to the framework, which proposed that repeated substance abuse resulted in brain changes that perpetuated the cycle of addiction. The findings emphasized the need for further research on the neurobiological effects of CUD in humans. In turn, it may provide a better understanding of which treatment options to employ.

May Lower IQ. A 2012 study published in the Proceedings of the National Academy of Sciences found that persistent cannabis use among adults who started smoking early led to a neuropsychological decline in learning, memory, and executive function. To gather the data, researchers tracked more than 1,000 users from adolescence to midlife, then performed the necessary IQ tests over the years. Findings revealed that early-onset users were more likely to have lower IQ as adults.

May Impair Memory. A 2013 study published in the Schizophrenia Bulletin found that early-onset and cannabis use may lead to abnormalities in the brain structures related to working memory, which may then result in poor memory. Moreover, researchers concluded that the earlier the onset of CUD, the greater the risk of developing the cannabis-related brain malformations.

A more recent 2016 investigation filed in the Journal of the American Medical Association Internal Medicine also found that heavy, chronic cannabis users had worse verbal memory than non-users and those who smoked less. That was the conclusion of the researchers after sifting through a 25-year data of more than 5,000 individuals, then analyzing the long-term effects on memory and cognitive performance.

Higher Likelihood of Alzheimer’s. In 2017, a study published in the Journal of Alzheimer’s Disease found that individuals with CUD had a higher susceptibility of developing Alzheimer’s disease (AD). Researchers used brain perfusion SPECT to examine the blood supply to the AD-related areas in the brain. Compared to healthy non-users, participants with CUD had lower cerebral blood flow in several brain regions, including the hippocampus, which is a primary target of AD pathology.

May Worsen Mental Troubles. Long-term THC exposure may cause or exacerbate psychiatric disorders, including anxiety, depression, schizophrenia, and psychosis. For instance, a 2002 study revealed that frequent cannabis use in teenagers might later result in anxiety and depression. Meanwhile, a 2008 study posited that cannabis use might trigger schizophrenia in individuals who are already vulnerable to the disorder due to genetics. Finally, a 2014 study reported that the daily use of highly-potent cannabis might lead to an earlier onset of psychosis. These results were published in BMJ, World Psychiatry, and Schizophrenia Bulletin, respectively.

Influences the Circulatory System. Upon consuming THC, the heart rate increases while the blood pressure drops. Aside from this acute reaction, it may also have adverse long-term cardiovascular (CV) effects. For instance, a 2017 study published in the Journal of Thoracic Disorders cited sudden cardiac arrest, arrhythmia, ventricular tachycardia, and myocardial infarction (MI) as some of the possible CV-related issues caused by cannabis.

However, a 2018 review from the Annals of Internal Medicine claimed that there is not enough evidence supporting the role of cannabis in increasing CV risk. That was the conclusion of researchers after examining more than 20 observational studies published between 1975 and 2017. At any rate, while the findings are inconclusive, those with a history of CV diseases should consider the risk factors.

May Lead to Chronic Bronchitis. In a 2007 study published in the Thorax, cannabis smokers reported having chronic bronchitis symptoms on top of other respiratory complaints like wheezing, coughing, and chest tightness. The study made use of comprehensive questionnaires, tests, and high-resolution CT scans to assess the effects of cannabis smoke on the lung structure, function, and symptoms. It suggested that cannabis smoking may induce a dose-related impairment of the large airways, although it was rarely associated with macroscopic emphysema.

Moreover, a 2016 study published in the European Respiratory Journal found that reducing or quitting cannabis use could reduce the preexisting symptoms of chronic bronchitis, cough, sputum production, and wheezing.

Lower Life Satisfaction and Achievement. A 2014 study published in The Lancet Psychiatry reported that chronic THC use might have negative effects on individual psychosocial functioning, reducing overall satisfaction and achievement later in life. Moreover, the data revealed that heavy, persistent cannabis use before age 17 years increases the risk of having impaired developmental outcomes – including educational attainment, depression, and suicide attempts – as adults. These effects appear to be dose-dependent.

A more recent 2017 research published in the Clinical Psychological Science supported these results. After keeping an eye on more than 1,000 individuals from birth to age 38 years, researchers found that those with CUD were more likely to have economic and social problems, including downward social-class mobility, financial difficulties, antisocial behavior in the workplace, and relationship conflicts.

THC Has Far-Reaching Effects On The Brain And The Body

Although other cannabis compounds are coming to light, THC remains as the most widely known and studied. With the wealth of scientific research available, it is slowly becoming more and more understood. For one, aside from being a prized recreational and psychotropic substance, THC also produces a variety of effects on the brain and the body, making it a valuable commodity for medical users. On the flip side, though, science has also revealed its unpleasant acute and chronic effects.

THC Effect

Despite the growing pool of studies, though, so much about it remains unknown and unclear. For instance, cannabis could exert a contradicting mechanism on certain conditions, and can both ameliorate and worsen it. Then, while science points to the dangers of its use, most of the evidence only found association instead of causality. In many instances, the results are inconclusive, and such inadequacy is due to the study design itself. Given all these, it can be hard to tell if THC is liable for the detrimental effects.

Even with the inconsistencies, a few things remain clear. One, the medicinal properties of THC cannot be ignored. Second, excessive use is bound to produce acute but possibly alarming upshots, which highlights the need for slow, careful dosing. Lastly, early, heavy, and chronic use is linked to unpleasant health impacts. Thus, while research aims to understand the mechanism of the phytochemicals better, it is crucial to consume responsibly and to steer clear of it during the teenage years or when predisposed to specific ailments. This way, the therapeutic benefits can be experienced while minimizing or eliminating the side effects.

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