Uncomfortable physical effects

Cardiovascular effects are defined as any uncomfortable physical effect which relates to the heart and blood vessels.

This page lists and describes the various cardiovascular effects which can occur under the influence of certain psychoactive compounds.

Abnormal heartbeat

Abnormal heartbeat (also called an arrhythmia or dysrhythmia) is defined as a problem with the rate or rhythm of a heartbeat.^[1] A heartbeat that is too fast (greater than 100 beats per minute) is called tachycardia and a heartbeat that is too slow (less than 60 beats per minute) is called bradycardia. Arrhythmias are caused by changes to heart tissue. Hearts beat due to cascading electrical signals and these can be influenced by stress hormones, electrolytes, and medicinal substances.

An abnormal heartbeat is most commonly induced under the influence of moderate dosages of stimulant and depressant compounds, such as cocaine,^{[2][3][4][5][6][7][8]} amphetamines,^{[9][10][11][12][13]} alcohol,^[13] and opioids.^[13][14][15] While stimulants tend to increase a person's heart rate, depressants tend to decrease it. Combining the two can often result in dangerously irregular heartbeats.

Decreased blood pressure

Decreased blood pressure can be described as a condition in which the pressure in the systemic arteries is decreased to abnormal levels. A blood pressure of 120/80 is considered normal for an adult. A blood pressure of 90/60 or lower is considered hypotension and a blood pressure between 120/80 and 90/60 is considered prehypotension.^[16]

Decreased blood pressure is most commonly induced under the influence of moderate dosages of GABAergic depressant compounds, such as benzodiazepines and barbiturates. However, it can also occur under the influence of vasodilating compounds such as poppers as well as certain psychedelics and stimulants in an unpredictable manner.

Decreased heart rate

Decreased heart rate or bradycardia can be described as a heart rate that is lower than the normal heart rate at rest. The average healthy human heart normally beats 60 to 100 times a minute when a person is at rest. When the heart rate fluctuates to lower levels under 60 BPM, it is described as bradycardia or an abnormally low heart rate.

It is worth noting that decreased heart rate can often be a result of psychological symptoms as a natural response to relaxation, anxiety suppression, sedation, and mindfulness.

Decreased heart rate is most commonly induced under the influence of heavy dosages of depressant compounds, such as GABAergics, and opioids. However, it can also occur under the influence of cannabinoids, dissociatives, and stimulants.

Increased blood pressure

Increased blood pressure can be described as a condition in which the pressure in the systemic arteries is elevated to abnormal levels. A blood pressure of 120/80 is considered normal for an adult. A blood pressure of 90/60 or lower is considered hypotension and a blood pressure between 120/80 and 90/60 is considered prehypotension.^[17] Conversely a blood pressure greater than 120/80 and less than 139/89 is considered prehypertension.

Within the medical literature, a situation in which a person's blood pressure is very high (e.g., >180/>110 mmHg) with minimal or no symptoms, and no signs or symptoms indicating acute organ damage is referred to as a "hypertensive urgency".^[18] In contrast, a situation where severe blood pressure is accompanied by evidence of progressive organ or system damage is referred to as a "hypertensive emergency".

Increased blood pressure is most commonly induced under the influence of heavy dosages of vasoconstricting compounds, such as traditional stimulants and stimulating psychedelics.

Increased heart rate

Increased heart rate or tachycardia is described as a heart rate that is faster than the normal heart rate at rest. The average healthy human heart normally beats 60 to 100 times a minute when a person is at rest. When the heart rate fluctuates to higher levels over 100 BPM, it is described as tachycardia or an abnormally high heart rate.

It is worth noting that increased heart rate can often be a result of psychological symptoms as a natural adrenal response to anxiety, paranoia, shock, and fear.

Increased heart rate is most commonly induced under the influence of heavy dosages of stimulating compounds, such as traditional stimulants, certain psychedelics, and certain dissociatives. This is thought to occur as a direct result of dopaminergic or adrenergic modulation.^[19][20] However, it can also occur under the influence of deliriants due to the way in which they inhibit acetylcholine, one of the main modulaters of heart rate in the peripheral nervous system.^[21][22]

Vasoconstriction

Vasoconstriction can be described as a narrowing of the veins and blood vessels which results from a contraction of their muscular wall. It is particularly prevalent in the large arteries and small arterioles.

This effect typically results in feelings of tightness, achiness, and numbness within a person's arms and legs. It can range from mild in its effects to extremely uncomfortable.

Vasoconstriction is often accompanied by other coinciding effects such as stimulation. It is most commonly induced under the influence of moderate dosages of stimulating psychedelic compounds, such as LSD, 2C-E, and DOC. However, it can also occur under the influence of traditional stimulants such as methamphetamine, caffeine, and MDMA.

Vasodilation

Vasodilation can be described as a widening of the veins and blood vessels which results from the relaxation of smooth muscle cells within the vessel walls. It is particularly prevalent in the large arteries and small arterioles. The primary function of vasodilation is to increase blood flow in the body to tissues that need it most. In essence, this process is the opposite of vasoconstriction, which is the narrowing of blood vessels.

This effect is typically very difficult to consciously perceive but often results in a bloodshot red eye effect and relief from glaucoma.

Vasodilation is often accompanied by other coinciding effects such as decreased blood pressure. It is most commonly induced under the influence of moderate dosages of cannabinoid compounds, such as cannabis, JWH-018, and THJ-018. However, it can also occur under the influence of poppers and viagra.

Cerebrovascular effects are defined as any uncomfortable physical effect which relates to the brain and its blood vessels.

This page lists and describes the various cardiovascular effects which can occur under the influence of certain psychoactive compounds.

Brain zaps

Brain zaps can be described as sharp electrical shock sensations which originate within the head or brain and sometimes extend throughout the body. For many people, it feels as though their brain has experienced a sudden series of brief vibrations or jolts of electricity that can cause intense discomfort, disorientation, and distress.

Brain zaps are most commonly induced under the influence of withdrawal, dose reduction, and discontinuation of antidepressant drugs, including selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs) such as sertraline, paroxetine, and venlafaxine. Tramadol, an opioid painkiller with SNRI properties, has also been reported to cause brain zaps upon abrupt discontinuation.^[23] If caused by antidepressant withdrawal, it is strongly recommended that one taper or reduce their dose gradually instead of stopping abruptly. This effect has been reported by anecdotal sources to occur in the days after a heavy dosage of MDMA.

Remedies to lessen the intensity or frequency of induced brain zaps include hydration (drinking enough water), supplementing for possible nutrient, vitamin or mineral deficiencies, getting adequate amounts of sleep, rest and stress relief.^{[citation needed]}

Additionally, several compounds and nutrients have been reported to possibly provide temporary relief from this affliction, although scientific literature supporting this claim is sparse.^{[citation needed]} The list includes:

• Magnesium
• Fish Oil (Omega 3)
• Melatonin
• 5-HTP (5-HTP might paradoxically increase brain zaps, this substance should be taken with consideration)
• L-Tryptophan
• GABA
• Agmatine
• Spirulina
• B-Vitamin Complex, but without Vitamin B12
• Diphenhydramine
• Huperzine A

Dizziness

Dizziness can be described as the perception of a spinning or swaying motion which typically causes a difficulty in standing or walking. It is commonly associated with a loss of balance and feelings of lightheadedness.

Within the medical literature, this effect is considered to be capable of manifesting itself across the 3 variations described below:

1. Objective - The first is known as objective and refers to when the person has the sensation that objects in the environment are moving.
2. Subjective - The second is known as subjective and refers to when the person feels as if they are moving.
3. Psuedovertigo - The third is known as pseudovertigo and refers to an intensive sensation of rotation inside the person's head.

Dizziness is often accompanied by other coinciding effects such as nausea and motor control loss. It is most commonly induced under the influence of heavy dosages of GABAergic depressant compounds, such as benzodiazepines, alcohol, and GHB. However, it can also occur to a lesser extent under the influence of heavy dosages of psychedelics, dissociatives, and cannabinoids.

Headaches

A headache can be described as a pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions. This occurs in migraines (sharp, or throbbing pains), tension-type headaches, and cluster headaches.^[24]

It is worth noting that due to its lacks of pain receptors, headaches are not caused by pain within the brain tissue itself, instead, headaches are caused by disturbances of the pain-sensitive structures around the brain.

Headaches are most commonly induced under the influence of heavy dosages of stimulating compounds, such as traditional stimulants, certain psychedelics, and certain dissociatives. This holds particularly true during the offset of the experience and if the person is dehydrated or has not eaten enough food.

Increased bodily temperature

Increased bodily temperature or pyrexia can be described as having a body temperature which is above normal baseline. While there is no universally agreed upon value at which pyrexia occurs, its diagnoses ranges between 37.5 - 38.3°C (99.5 - 100.9°F). For comparison, the average temperature of a healthy person is around 37°C (98.6°F). It is worth noting that a bodily temperature which exceeds 41.5°C (106.7°F) is an emergency which requires immediate medical attention and can potentially result in physical injury, long-term side effects, and death.

This effect is capable of manifesting itself in the two different forms which are described below:

• Fever is used to describe the body raising its core temperature due to illness. For example, a fever may be caused by a bacterial infection.
• Hyperthermia is classified as an uncontrollable increase in body temperature that typically originates from an external source. This most frequently involves heat strokes or the use of certain drugs.

Increased bodily temperature is often accompanied by other coinciding effects such as increased perspiration, dehydration, headaches, and serotonin syndrome. It is most commonly induced under the influence of heavy dosages of stimulant compounds which affect serotonin and 5-HT receptors^[25], dopamine and D receptors^[26] and norepinephrine^[27]. These substances include amphetamine, methylphenidate, MDMA, and cocaine. However, it can also occur under the influence of certain stimulating psychedelics such as AMT, 2C-P, and DOC.

Seizure

An epileptic seizure (colloquially a fit) can be described as a brief episode of signs and/or symptoms which are due to abnormal, excessive, or synchronous neuronal activity in the brain.^[28] The outward effect can vary from uncontrolled jerking movement (tonic-clonic seizure) to as subtle as a momentary loss of awareness (absence seizure).

The following list contains a more comprehensive set of symptoms:

• Losing consciousness and then exhibiting confusion afterwards.
• Having uncontrollable muscle spasms which often result in falling.
• Drooling or frothing at the mouth.
• Jaw clenching and tongue biting.
• Having sudden, rapid eye movements.
• Making unusual noises, such as grunting.
• Losing control of bladder or bowel function.

The disease of the brain characterized by an enduring predisposition to generate epileptic seizures is known as epilepsy,^[28][29] but seizures can also occur in people who do not have epilepsy. Depending on the cause, epilepsy is generally treated with anticonvulsant drugs such as diazepam and pregabalin.

Seizures are most commonly induced under the influence of withdrawals from prolonged chronic benzodiazepine or alcohol usage. However they can also occur under the influence of moderate dosages of stimulants, certain opioids, synthetic cannabinoids, and the 25x-NBOMe series of psychedelics.

Temperature regulation suppression

Temperature regulation suppression can be defined as an inability to maintain a normal temperature. This results in feelings of constantly fluctuating between being uncomfortably cold^[30] and uncomfortably hot. At points, this can even result in the sensation of being uncomfortably warm and cold simultaneously.

Temperature regulation suppresion is often accompanied by other coinciding effects such as stimulation and increased perspiration. It is most commonly induced under the influence of heavy dosages of stimulating psychedelic compounds, such as LSD, 2C-B, and AMT. However, it can also occur under the influence of stimulants such as MDMA and methamphetamine.

Uncomfortable bodily effects are defined as any uncomfortable physical effect which relates to the overall body and cannot be categorized as cardiovascular or cerebrovascular.

This page lists and describes the various uncomfortable bodily effects which can occur under the influence of certain psychoactive compounds.

Back pain

Back pain can be described as feelings of aches and pain located throughout a person's back. It may occur as neck pain (cervical), middle back pain (thoracic), lower back pain (lumbar), or coccydynia (tailbone or sacral pain). However, the lumbar region is the most common area for pain, as it supports most of the weight in the upper body. The pain itself can range from mild and ignorable to intense and distinctly uncomfortable.

Within the context of psychoactive substances, this effect can occur through tactile enhancement which increases the symptoms of a pre-existing condition which is usually otherwise not noticeable, as a result of muscle tension, as a result of kidney problems^{[citation needed]}, and also as a symptom of withdrawal symptoms from substances which are used for pain relief such as opioids.

Back pain is most commonly induced under the influence of heavy dosages of stimulating psychedelic compounds, such as LSD, 2C-B, and mescaline.

Bodily pressures

Bodily pressures can be described as the physical experience of spontaneous pressures across differing parts of the body. These can occur as static and fixed in their location or they can occur at seemingly random varying points across the body. Depending on the intensity of the sensation, this can result in pressures which range from neutral to extremely uncomfortable in their experience.

Bodily pressures are most commonly induced under the influence of heavy dosages of stimulating psychedelics, such as 2C-E, DPT, and 5-MeO-DMT.

Constipation

Constipation can be described as bowel movements that are infrequent or hard to pass. It usually results in painful defecation and small, compact faeces. Symptoms of substance constipation may be reduced by increasing the amount of dietary fruit, fibre, and water consumed. Laxatives may also be used for temporary relief.

Constipation is often accompanied by other coinciding effects such as nausea, dehydration, and difficulty urinating. It is most commonly induced under the influence of heavy dosages of opioid compounds, such as heroin, tramadol, fentanyl, and kratom.

Dehydration

Dehydration can be described as an uncomfortably dry mouth and feelings of general thirstiness that results due to a lack of water intake. Untreated dehydration generally results in delirium, unconsciousness, swelling of the tongue, and (in extreme cases) death. The formal definition of dehydration is defined as an excessive loss of body water within a living organism which results in an accompanying disruption of metabolic processes.

At lower levels, substance-induced dehydration can be generally described as a sense of consistent and uncomfortable thirst which necessitates sipping at a drink to maintain fluid levels and to avoid an uncomfortably dry mouth. At extreme levels (which generally only occur through the use of deliriants), the dehydration can become so powerful that the person may find themselves with painfully dry eyes and mucous membranes in a manner which results in extreme difficulty swallowing.

Dehydration is often accompanied by other coinciding effects such as dry mouth, headaches, dizziness, decreased blood pressure, and fainting when standing up. It is most commonly induced under the influence of moderate dosages of a wide variety of compounds such as, stimulants, psychedelics, opioids, dissociatives, deliriants, cannabinoids, alcohol, and antipsychotics.

Water intoxication

It's important to note that regardless of how dehydrated a person may become under the influence of any substance, careful effort and consideration should always be put into ensuring that they do not drink water excessively as it can result in a state known as water intoxication. This can be potentially fatal and is classed as a disturbance in brain functions that results when the normal balance of electrolytes in the body is pushed outside of safe limits by over-hydration. Although extremely rare, there have been a few notable deaths which were clearly triggered by the excessive overconsumption of water under the influence of drug-induced dehydration.

The average toxic dosage of water in a human being is roughly ten litres. However, water intoxication can be easily avoided by simply being aware of it and taking care to sip at water while avoiding the consumption of unnecessarily large amounts.

Diarrhea

Diarrhea or diarrhoea is the condition of having at least three loose or liquid bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. This can progress to decreased urination, loss of skin colour, a fast heart rate, and a decrease in responsiveness as it becomes more severe. In the context of psychoactive substance usage, certain compounds have been known to induce diarrhea or can at least increase the likelihood of it occurring.^[31][32][33] This is not as dangerous as the same condition when it occurs through infection as it only remains until the person is no longer under the influence of the drug.

Diarrhea is often accompanied by other coinciding effects such as nausea and dehydration. It is most commonly induced under the influence of heavy dosages of certain psychedelic compounds, such as ayahuasca, mescaline, and psilocybin mushrooms. However, it can also occur under the influence of certain stimulants, modafinil, and caffeine.

Difficulty urinating

Difficulty urinating also known as urinary retention, can be described as the experience of a decreased ability to pass urine. This can be due to painful burning sensations within the urethra or a due to a loss of bladder control which prevents or inhibits one from urinating even with a full bladder.

Difficulty urinating is often accompanied by other coinciding effects such as stimulation and constipation. It is most commonly induced under the influence of heavy dosages of stimulant and opioid compounds, such as heroin, fentanyl, kratom, amphetamine, MDMA (Death of Leah Betts), and 4-FA. However, it can also occur under the influence of stimulating psychedelics and deliriants.

Dry mouth

Dry mouth (also known as xerostomia) is defined as having a dry-feeling mouth, often accompanied by a difficulty swallowing. It is usually a direct result of dehydration but can be felt to occur regardless of the actual dryness of a person's mouth.

Chronic xerostomia or "dry mouth syndrome" is the regular and/or consistent experience of having a dry mouth that can result due to natural causes or as a product of the prolonged usage of mouth-drying substances. To treat this condition, substances such as cevimeline which stimulate the release of saliva are typically used. However, a problem noted with repeated use of such treatments is the overall worsening of the dry mouth symptoms over time. If the body adjusts to having chemical assistance in increasing saliva production cessation of treatment with the chemical can lead to physiological dependence wherein there is a rebound effect upon abrupt stopping of treatment.

In general, if the cause of dry mouth is due to a psychoactive substance, medication, or combination, medical treatment is not recommended. Dry mouth as an effect of substances is considered to be benign unless the effect is chronic and continues to bother or cause tooth/gum issues in the person experiencing it. As a basic harm reduction practice one should be mindful to stay consistently well hydrated, avoid breathing through the mouth, and limit substance usage if the effect becomes uncomfortable, unmanageable, or persists even when not under the influence of a psychoactive substance.

Dry mouth is often accompanied by other coinciding effects such as frequent urination (due to drinking excessive amounts of water) and dehydration. It is most commonly induced under the influence of moderate dosages of a wide variety of compounds, such as stimulants, psychedelics, opioids, antispychotics, deliriants, SSRI's, and cannabinoids. It is also a common side effect of many substances, especially the combination of more than one substance which can produce or amplify already present experience of a dry mouth, which can interact significantly.

Frequent urination

Frequent urination, or urinary frequency, can be defined as the need to urinate more often than usual. It is often, though not necessarily, associated with urinary incontinence and large total volumes of urine. However, in other cases, urinary frequency involves only normal volumes of urine overall.

Frequent urination is often accompanied by other coinciding effects such as dehydration and dry mouth in a manner which further amplifies the needs to urinate through excessive consumption of water. It is most commonly induced under the influence of moderate dosages of a wide variety of compounds, such as stimulants, psychedelics, dissociatives, and deliriants.

Increased perspiration

Increased perspiration, or hyperhidrosis, can be described as a condition characterized by increased sweat which is in excess of that required for the regulation of body temperature.

Increased perspiration is a hallmark symptom of sympathetic arousal (the "fight-or-flight" response) and is a common effect of stimulant drugs. Any psychoactive drug which exerts considerable serotonergic, dopaminergic, or adrenergic effects may cause increased perspiration. It is also a common symptom of benzodiazepine and alcohol withdrawal. Cholinergics and, to a lesser extent, opioids have been additionally implicated in causing this as well.^{[citation needed]}

Increased phlegm production

Increased phlegm production can be described as the experience of the throat and respiratory system producing excessive amounts of mucous fluid that is often expelled via coughing. This typically feels as if a person's throat and the back of the mouth are becoming repeatedly filled with a thick slime like substance which needs to be either periodically swallowed or spat out to avoid discomfort.

Increased phlegm production is often accompanied by other coinciding effects such as excessive yawning, increased salivation, a runny nose, and watery eyes. It is most commonly induced under the influence of heavy dosages of tryptamine psychedelic compounds, such as psilocybin, 5-MeO-MiPT, 4-AcO-DMT, and 4-HO-MET.

Itchiness

Itchiness is the sensation that causes a person the desire or reflex to scratch at their skin. At lower levels, itchiness can occur as a subtle and minor annoyance which is easy to ignore. However, at higher levels, itchiness can become so intense that is incredibly uncomfortable and can even result in the person damaging their skin through repetitive scratching motions.

Itchiness is most commonly induced under the influence of heavy dosages of opioid compounds, such as heroin, fentanyl, tramadol, and kratom. This is due to the way in which opioids activate histamine receptors and trigger histamine release. An effective technique for counteracting itchiness in cases of substance use is to take an antihistamine such as diphenhydramine (DPH, Benadryl).

Muscle cramps

A muscle cramp can be described as an involuntary temporary contraction or over shortening of muscles which may cause severe aches and pains. The onset of these muscle cramps is usually sudden while the cramp typically resolves itself spontaneously within a few seconds or minutes.

Muscle cramps are often accompanied by other coinciding effects such as muscle twitching and stimulation. They are most commonly induced under the influence of heavy dosages of stimulating psychedelic compounds, such as LSD, 2C-E, DOC, and AMT. However, they can also occur under the influence of certain GABAergic depressants such as GHB and phenibut.

Muscle cramps may be avoided with supplements including: Magnesium (preferably glycinate), and/or vitamin B complex.^{[citation needed]}

Muscle twitching

Muscle twitching can be described as the sensation of small and localised tremblings of muscle groups. These vibrations are often powerful enough to be visibly seen through the skin. The sensations they induce can be uncomfortable in certain contexts but are usually neutral to experience.

Muscle twitching is most commonly induced under the influence of moderate dosages of stimulating psychedelic compounds such as LSD, 2C-E, DOC, and AMT. However, it can also occur under the influence of traditional stimulants.

Muscle tension

Muscle tension can be described as extended partial contractions or over shortening of muscles which can cause persistent low-level aches and pains. Muscle tension is typically caused by the physiological effects of stress and can lead to episodes of back pain.

Muscle tension is often accompanied by other coinciding effects such as muscle twitching and muscle cramps. It is most commonly induced under the influence of heavy dosages of stimulating psychedelic compounds, such as LSD, 2C-E, DOC, and AMT. However, it can also occur under the influence of certain GABAergic depressants such as GHB and phenibut.

Nausea

Nausea can be described as a sensation of unease and discomfort in the upper stomach combined with an involuntary urge to vomit.^[34][35][36] It often, but not always, precedes vomiting. This effect usually occurs at the onset of the experience and dissipates as the peak takes its toll.

In the context of substance usage, nausea and vomiting can occur as a result of stomach irritation through the consumption of materials which it is not used to digesting. These materials can include things such as chemical powders or plant matter. Alternatively, nausea may occur as a direct pharmacological result of how the particular substance affects the brain. If this is the case, the nausea is therefore inseparable from the experience itself and will likely occur to varying extents regardless of the route of administration.

Nausea is often accompanied by other coinciding effects such as stomach bloating, stomach cramps, and dizziness. It is most commonly induced under the influence of heavy dosages of a wide variety of compounds, such as psychedelics, opioids, GABAergics, deliriants, dissociatives, and stimulants.

Vomiting

Vomiting, also known as purging, puking and throwing up, among other terms, is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose. This effect typically occurs during the peak of a substance's effects. It can often greatly relieve the person's physical side effects once it is over. For example, under the influence of many hallucinogenic compounds, it is common for a person to feel that their trip has become significantly more enjoyable after the act of vomiting due to their uncomfortable stomach symptoms suddenly subsiding as a result.

It is worth noting that a person should not brush their teeth immediately after vomiting. This is because the corrosiveness of stomach acid combined with the abrasiveness of brushing can cause permanent damage to a person's teeth when repeated over time. Instead, a person should wash their mouth out with water, mouthwash, a water flosser, or a mixture of baking soda and water (to neutralise the acidity).

Optical sliding

Optical sliding can be described as a physical effect which inhibits the coordination and control of a person's eyes by suppressing their ability to keep them still. This results in the eyes continuously moving in a variety of directions combined with the sensation of not being able to stare motionless at any particular point.

The optical condition nystagmus causes sufferers very similar symptoms, although the frequency of movement is generally far greater with nystagmus.

Optical sliding is often accompanied by other coinciding effects such as visual acuity suppression and double vision. It is most commonly induced under the influence of heavy dosages of dissociative compounds, such as ketamine, PCP, and DXM. However, it can also occur to a lesser extent under the influence of extremely heavy dosages GABAergic depressants.

Photophobia

Photophobia can be described as an abnormal physical intolerance to the visual perception of light. As a medical symptom, photophobia is not a morbid fear or psychological phobia, but an experience of discomfort or pain to the eyes due to light exposure.

Photophobia is almost always accompanied by other coinciding effects such as pupil dilation which may trigger this effect by disabling the eye's ability to adjust itself accordingly depending on current levels of light exposure. It is most commonly induced under the influence of heavy dosages of psychedelic compounds, such as LSD, psilocybin, and mescaline. However, it can also occur to a lesser extent under the influence of certain stimulants.

Physical fatigue

Physical fatigue can be described as a general feeling of bodily exhaustion. The intensity and duration of this effect typically depends on the substance consumed and its dosage. It can also be further exacerbated by various factors such as a lack of sleep or food. These feelings of exhaustion involve a wide variety of symptoms which generally include some or all of the following effects:

• Sedation
• Perception of bodily heaviness
• Decreased libido
• Motor control loss
• Sleepiness

People who are fatigued may find it difficult to complete physical actions and may not be capable of getting out of bed or performing everyday household tasks. It can generally be treated with a period of rest or sleep.

Physical fatigue is often accompanied by other coinciding effects such as cognitive fatigue. It is most commonly induced under the influence of moderate dosages of antipsychotic compounds, such as quetiapine, haloperidol, and risperidone. However, it can also occur during the withdrawal symptoms of many depressants, and during the offset of many stimulants.

Respiratory depression

Respiratory depression (also known as hypoventilation) can be described as a reduced urge to breathe that can be fatal depending on its intensity. At relatively safe levels, this effect typically causes a "sighing" pattern of breathing which can be described as deep breaths separated by abnormally long pauses. At higher levels, however, an individual may cease breathing entirely in a manner which is rapidly fatal without immediate treatment.

This effect is capable of manifesting itself across the 4 different levels of intensity described below:

1. Minimal respiratory depression - At the lowest level, respiratory depression is typically subtle enough to be unnoticeable and is accompanied by mild sedation.
2. Moderate respiratory depression - At this level, the person becomes aware of the sensation that they are taking fewer breaths per minute than usual. This level of respiratory depression is not uncomfortable and does not result in any shortness, struggling, or impairment of breath.
3. Severe respiratory depression - At this level, a person's rate of breathing becomes noticeably slowed down by a significant margin which results in the person feeling that they are breathing abnormally, are short of breath, and cannot breathe in enough air. This forcibly redirects the person's focal point of attention towards manually regulating their own breathing in order to not feel extremely uncomfortable. At this point, extreme sedation is usually also present and if sleep occurs the person can potentially wake up struggling and gasping for air. Confusion, panic, and anxiety often occur at this level, further increasing the strong sensation that one's breathing will stop completely due to sleep or a lack of attention.
4. Respiratory failure - At the highest level, the person's oxygen and carbon dioxide levels become dangerously impaired. The person will fall into a semi-conscious state, lose consciousness completely, slip into a coma, or stop breathing completely. The skin, fingernails, or lips may also have a blue-ish colour to them. This level of respiratory failure will likely be fatal without immediate medical attention.^[37] Opioids and barbiturates, in overdose or combined with other depressants, are notorious for such fatalities.

Respiratory depression is often accompanied by other coinciding effects such as sedation and sleepiness. It is most commonly induced under the influence of heavy dosages of depressant compounds, particularly opioids, such as heroin and fentanyl, or GABAergics, such as alcohol and GHB. However, it is worth noting that otherwise safe dosages of these compounds can become fatal when combined with even small amounts of other classes of depressant. For example, benzodiazepines combined with opioids are an extremely common cause of fatal respiratory depression. It is therefore strongly discouraged to combine these depressants at any dosage range.

Treatment

To prevent death, it is recommended to contact emergency medical services immediately in case of severe respiratory depression. If caused by an opioid overdose, an opioid antagonist, such as naloxone, should be administered. Many harm reduction organizations provide naloxone to users for free or it can be bought at pharmacies (including Walgreens and CVS in the U.S.). Naloxone will rapidly reverse the respiratory depression unless complicated by other depressants.

For other drug-induced respiratory depression, hospitalization and the assistance of a mechanical breathing machine may be necessary.

Restless legs

Restless legs (also known as restless legs syndrome or RLS) is a medically defined as an irresistible urge to move one's body to stop uncomfortable or odd sensations.^[38] It most commonly affects the legs but can also affect the arms, torso, and head. During this state, moving the affected body part reduces the uncomfortable sensations, providing temporary relief.

RLS sensations can range from pain, an aching in the muscles, "an itch you can't scratch", an unpleasant "tickle that won't stop", or even a crawling feeling. The sensations typically begin or intensify during quiet wakefulness, such as when relaxing, reading, studying, or trying to sleep.

Restless legs syndrome is most commonly induced during the withdrawal symptoms of many depressants, such as opioids or benzodiazepines, and during the offset of many stimulants, such as methamphetamine, cocaine, and MDMA. However, it can also occur under the influence of deliriants such as DPH and datura.

Runny nose

A runny nose can be described as a condition where the nasal cavity is filled with a significant amount of mucous fluid, otherwise known as "snot". This occurs relatively frequently within healthy human beings and is a common symptom of allergies or certain diseases, such as the common cold or hay fever. It can also be a side effect of crying and exposure to cold temperatures.

A runny nose is often accompanied by other coinciding effects such as excessive yawning, increased salivation, increased phlegm production, and watery eyes. It is most commonly induced under the influence of heavy dosages of tryptamine psychedelic compounds, such as psilocybin, 4-AcO-DMT, and 4-HO-MET. However, it can also occur under the influence of opioid withdrawals^[39]) and as a symptom of cocaine abuse.^[40]

Skin flushing

Skin flushing can be described as the experience of a sudden reddening of the skin which is usually accompanied by feelings of rushing blood and warm skin. In terms of its appearance, it manifests itself in an identical although more intense fashion to that which occurs across the face when one is embarrassed. Blotchiness or solid patches of redness are also often visible during states of skin flushing.

Skin flushing is most commonly induced under the influence of heavy dosages of opioid compounds, such as heroin, tramadol, fentanyl, and kratom. However, it can also occur under the influence of alcohol, certain psychedelics such as 5-MeO-DMT, and stimulants, such as caffeine.

Stomach bloating

Stomach bloating can be described as an uncomfortable physical side effect which results in one's stomach becoming temporarily bloated and expanded in a manner which looks somewhat similar to pregnancy. This effect can be moderately uncomfortable but is not painful or dangerous. Its overall duration can last anywhere from a couple of hours to a couple of days and can be reduced by drinking plenty of water.

In the context of substance usage, stomach bloating can occur as a result of stomach irritation through the consumption of materials which it is not used to digesting. These materials can include things such as chemical powders or plant matter. Alternatively, stomach bloating may occur as a direct pharmacological result of how the particular substance affects the large amount of serotonin receptors present within the intestinal wall.

Stomach bloating is often accompanied by other coinciding effects such as nausea and vomiting. It is most commonly induced under the influence of heavy dosages of psychedelic compounds, such as LSD, psilocybin, and mescaline. However, it can also occur under the influence of stimulants, opioids, and depressants.

Stomach cramps

A stomach cramp can be described as an intense feeling of sudden pain or discomfort which occurs within the stomach.

In the context of substance usage, stomach cramps can occur as a result of stomach irritation through the consumption of materials which it is not used to digesting. These materials can include things such as chemical powders or plant matter. Alternatively, cramps may occur as a direct pharmacological result of how the particular substance affects the brain. If this is the case, the stomach cramps are therefore inseparable from the experience itself and will likely occur to varying extents regardless of the route of administration.

Stomach cramps are often accompanied by other coinciding effects such as stomach bloating, nausea, and vomiting. They are most commonly induced under the influence of heavy dosages of a wide variety of compounds, such as psychedelics, opioids, GABAergics, and deliriants.

Teeth grinding

Teeth grinding (also known as bruxism, jaw clenching, and gurning) can be described as a compulsive and often uncontrollable urge to grind one's teeth. In extreme cases, this can result in painful damage to one's tongue, teeth and inner cheek.

The most effective methods for quickly alleviating uncomfortable teeth grinding include using chewing gum or a baby's pacifier (also called a dummy) to occupy one's jaws without causing damage. Magnesium, preferably magnesium glycinate, is also very effective at alleviating bruxism when it is taken at a dosage of 200mg once 6 hours before and again at 1-3 hours before ingesting a stimulant such as MDMA or amphetamine.^[41]

Teeth grinding is often accompanied by other coinciding effects such as stimulation and wakefulness. It is most commonly induced under the influence of common dosages of stimulant compounds, such as methamphetamine, MDMA, methylphenidate, and cocaine. However, it can also occur under the influence of certain stimulating psychedelics such as 2C-E, DOC, and AMT.

Temporary erectile dysfunction

Temporary erectile dysfunction can be described as a difficulty in achieving and maintaining an adequately erect penis for the purpose of sexual intercourse. This effect occurs under the influence of certain substances in various degrees of intensity.

Temporary erectile disfunction is often accompanied by other coinciding effects such as stimulation, difficulty urinating, and temperature regulation suppression in a manner which further amplifies the problem. It is most commonly induced under the influence of heavy dosages of stimulating compounds, such as traditional stimulants and certain psychedelics. However, it can also occur under the influence of opioids, dissociatives, GABAergics, and deliriants.

Vibrating vision

Vibrating vision, also known as nystagmus, can be described as the experience of constant, rapid involuntary eye movements in which the eyes shift from left to right in such quick succession that the person's vision begins to vibrate and blur. This can severely impair vision and result in a reduced ability to function and perform basic tasks which necessitate the use of sight.

Vibrating vision is often accompanied and enhanced by other coinciding effects such as stimulation and thought acceleration. It is most commonly induced under the influence of heavy dosages of stimulant compounds, such as MDMA, amphetamine, and 4-FA.

Watery eyes

Watery eyes can be described as a physical effect which results in a state of continuous involuntary streaming, tearing, crying, and watering of the tear ducts within one's eyes. The experience of this effect often leads to the feeling that a person is crying for no reason despite a complete absence of the relevant emotions one would usually expect during such a state.

Watery eyes is often accompanied by other coinciding effects such as excessive yawning and a runny nose. It is most commonly induced under the influence of moderate dosages of psychedelic tryptamine compounds, such as psilocybin, 4-AcO-DMT, and 4-HO-MET.