Marijuana

Compared to non-smokers, people who smoked cannabis regularly in adolescence exhibit reduced connectivity in specific brain regions associated with memory, learning, alertness, and executive function. 

Its regular use is associated with a decrease in short-term memory and cognitive function, and poor school work or work performance, mood disorders and psychosis.

The operation of airplanes, automobiles, motorcycles, trains and its effects are dose dependent.

Automobile accidents occur 2-7 times more frequently when using marijuana.

Cannabis use is associated with impaired driving ability within an associated increase of risk of motor vehicle crashes of 30-40%, compared to blood alcohol concentrations of .08%, which increases the risk of crashes by 250 to 300%.

There is evidence of permanent neurological changes associated with marijuana use that begins prior to age 21: adverse effects on executive function, memory, and verbal deficits.

There is an average six point decrease in intelligence quotient from childhood to adulthood comparing marijuana users with non-users.

Worldwide estimated 178 million people aged 15-64 years used marijuana at least once in 2012.

Current market is approximately 7% of Americans.

Use has more than doubled.

Whether used for recreational or medicinal purposes, people can develop marijuana withdrawal symptoms.

Withdrawal symptoms can include restlessness, irritability, and sleep issues.

People who use marijuana regularly and then stop abruptly can experience some withdrawal symptoms.

Regular marijuana use can develop into marijuana use disorder, and severe cases, this can take the form of an addiction.

Marijuana withdrawal symptoms peak within the first week of quitting and can last up to 2 weeks.

Symptoms of marijuana withdrawal can include:

irritability

difficulty sleeping

decreased appetite

restlessness

cravings for marijuana

nausea

abdominal pain

THC defines the potency of marijuana.

Most cannabis products contain several hundred substances among 18 different chemical classes including terpenes, flavonoids, and alkaloids, in addition to more than 100 reported cannabinoids, which are the most characteristic compounds of cannabis.

Pyrolysis produces many other substances.

The more THC the marijuana contains, the greater the effect of marijuana on the brain.

Using marijuana regularly means that the brain and body get used to a regular supply of THC.

When this supply is stopped, it causes uncomfortable physical and psychological withdrawal symptoms.

When the brain and body adjusts to not having THC, the physical withdrawal symptoms will stop.

Current effects of marijuana, including withdrawal, may be more extreme compared with their effects in previous decades due to the higher content of THC.

After quitting marijuana, it can take a month for the brain to return to normal function.

The mood difficulties and physical discomforts of withdrawal peak in the first week of quitting and can last up to 2 weeks.

While the physical effects of marijuana withdrawal stop after the drug has left a person’s system, the psychological symptoms can last longer.

Cannabinoid 1 brain receptors start to return to normal after 2 days without marijuana.

The  endocannabinoid system comprises of two cell surface receptors – cannabinoid receptors type one (CB1) and type two (CB2)

Cannabinoid 1 brain receptors regain normal functioning within 4 weeks of stopping the drug.

CB1 receptors are predominately expressed in the CNS, while CB2 receptors are primary expressed in the immune system.

CB1 receptors are found on both neurons and glia throughout the brain, especially in regions that are thought to mediate prominent effects of THC, such as the hippocampus, basal ganglia, cerebellum, cerebral cortex.

Adults who use cannabis over a long-term have down regulation of the brain CB1 receptors.

CB1 receptors are also found outside the CNS in the myocardium, vascular endothelium, adipose tissue, the liver, and the reproductive organs.

CB2  receptors were found primarily on immune cells, although some are in the CNS.

THC is rapidly absorbed when inhaled, appearing in plasma within seconds, with peak concentration, occurring 5 to 10 minutes.

in contrast, oral THC results in slow absorption, with peak plasma concentration occurring in 2 to 6 hours.

People may feel cravings for marijuana after they have stopped using the drug.especially in contexts and settings where they are used to using marijuana.

According to the CDC, research has linked marijuana use with numerous negative health consequences: memory problems, an increased risk of stroke and heart disease,  myocardial infarction,  lung problems from marijuana smoke, and mental health symptoms such as those related to anxiety and paranoia.

Compared with non-uses daily cannabis consumers had a 25% higher odds of myocardial infarction, and 42% higher risk of stroke.

More frequent use of cannabis is associated with greater possibility of adverse cardiovascular outcomes regardless of whether cannabis was smoked, eaten, or vaporized.

An analysis of more than 2 million cannabis users within the US suggests those with arrhythmia were 4.5 times more likely to die during hospitalization than those without an arrhythmia.

People who used cannabis visited emergency rooms or were hospitalized 22% more often than those who did not use cannabis, in a recent Canadian study.

National Inpatient Sample (NIS) identified adult hospitalizations with a diagnosis of cannabis use related disorders and arrhythmias.

Of  2,457,544 hospitalizations associated with cannabis use related disorders, 7.6% were associated with any arrhythmia.

Among those with arrhythmias, atrial fibrillation was the most common, appearing in more than 40% of patients

There is substantial evidence in both animal and human studies that marijuana exposure early in life can result in cognitive impairments such as problems with memory, learning, and altered reward systems in the brain ( National Institute on Drug Abuse).

Over 300,000 people begin treatment for marijuana use disorders in the U.S. each year.

Over the years, based on samples of confiscated marijuana, potency has steadily increased, to being greater than 12%.

Legalization does not seem to have significantly increased marijuana use.

It is possible to become dependent on, or even addicted to, marijuana with regular use.

Prevalence is about 31% among those 18-34 years.

The criteria for marijuana use disorder has increased from 1 1/2 to 2.9%.

Cannabis use among the pregnant women has increased significantly over the last four decades.

7.5%, 19.8 million, of US individuals aged 12. years or older report use on 2013.

Cannabis sativa, a hemp plant is the source.

Marijuana is the name for dried extracts from the plant Cannabis sativa.

This plant contains delta-9-tetrahydrocannabinol (THC), which is the substance that causes the psychoactive effects associated with marijuana use.

delta-9-tetrahydrocannabinol (THC)results in euphoric, psychoactive effects that characterize marijuana as a drug of abuse.

THC acts via CB1 receptor, that is found widely in the brain and body.

CB1 can activate euphoria, but little is known of its activities in other areas of the brain and body.

Cannabis has numerous cannabinoids but only a few have high-quality evidence to support their use and are approved for medicinal use by the FDA.

There is only inconclusive evidence cannabinoids effectively manage chronic pain, and large numbers of patients must receive treatment with cannabinoids for a few to benefit, while not many need to receive treatment to result in harm (Hill KP).

There is insufficient evidence to support or refute claims that marijuana provides relief for spinal cord injury-related muscle spasms.

Cannabinoids dronabinol and nabilone are approved for chemotherapy induced nausea and vomiting and dronabinol is used for appetite stimulation that causes weight loss in situations such as AIDS.

Cannabidiol is approved for two forms of pediatric epilepsy patients-Dravet syndrome and Lennox-Gastaut syndrome

Parts of the plant vary in potency, with the top of the female plant being most potent.

Comprises more than 60 pharmacologically active cannabinoids.

Abuse/dependence prevalence in an inpatient setting approximately 1 1/2%.

Abuse/dependence has an increasing trend in older and sicker patients.

The most common comorbidities are psychiatric illness and alcoholism.

Cannabis abuse associated with an increase in asthma in nontobacco smokers.

Heavy cannabis use associated with low bone mineral density and increased risk of fractures.

Cannabinoids act on cannabinoid receptors located throughout the body but mostly in the brain and spinal cord.

The endogenous cannabinold system regulates neuronal excitability and inflammation in pain circuits and helps regulate movement, appetite, aversive memory extinction, hypothalamus-pituitary-adrenal axis modulation, immunomodulation, mood, wake/sleep cycles, blood pressure, bone density, tumor surveillance, neuroprotection, reproduction, “runners high” effects.

The endogenous cannabinoid system is common to all vertebrates.

Available in forms they can be smoked, vaporized, or ingested.

Its mean active ingredient is tetrahydrocannabinol (THC), which produces psychoactive effects, euphoria, reduced anxiety, improved mood, and stimulation of appetite.

Activation of two types of G protein-coupled receptors CB1and Cb2 exerting actions by directly inhibiting the release of multiple neurotransmitters including acetylcholine, dopamine, and glutamate while indirectly affecting gamma aminobutyric acid, N-methyl-D-aspartate, opioid, and serotonin receptors.

CB1 receptors are concentrated primarily in the basal ganglia, cerebellum, hippocampus, spinal cord, and peripheral nerves.

CB1 receptors are the most abundant G-protein-coupled receptors in the brain and are expressed at lower densities in many peripheral tissues.

CB1 receptors mediate psychotropic behavioral effects of cannabis and regulate several peripheral processes such as energy homeostasis, cardiovascular function, and reproduction.

CB1 distribution in the gray matches its pharmacodynamic effects cognition, memory, perception, control of motor function, and analgesia.

CB2 receptors are found mainly on cells in the immune system, affecting marijuana’s effects on pain and inflammation.

CB2 is on immune cells including macrophages, lymphocytes, microglia of the CNS, and osteoclasts.

CB2 receptor expression can be induced on neurons in states of injury and inflammation.

CB2 receptors are sparsely expressed in the CNS.

CB2 receptor activation modulates immune cell migration and cytokine release.

CB2 receptor expression on CNS microglia can explain cannabis’ efficacy in reducing cytokine-mediated neuroinflammation.

CB2 activation does not result in euphoria or psychotropic events, and may play a role in reducing rewarding activities of substances of abuse like cocaine and opioids.

Cannabinoids receptor activation reduces locomotor function, has a antispasmatic effect, pain relieving effect, can cause euphoria, psychosis, impaired memory, impaired cognition, and sleep promoting effect

The major cannabinoids in marijuana are Delta9-tetrahydrocannabinol (THC) and cannabidol.

THC causes euphoria and can produce psychosis.

Cannabidol is not psychoactive but has a anti-anxiety and possible antipsychotic effects.

The therapeutic effects of marijuana lies in the THC effect but the ratio of THC to cannabidol is also important.

The primary active cannabis constituent is THC.

Can be administered orally, sublingually, or topically and smoked, inhaled, in food, or as a tea.

Smoking releases everything in the leaf including tar, which may produce negative health effects

The vaporized leave releases selective cannabinoids and is preferred for medicinal use.

The vaporized form effects peak in approximately five minutes and they last about two hours.

Effects of oral ingestion may last 6 to 8 hours, but there is less control over the peak.

THC may be present in plasma and lipid depots in heavy users more than 24 hours following the last cannabis use.

Sublingual spray effects have a shorter duration, at approximately four hours, with the peak affect at one hour.

Can be prescribed for medical use in capsules, or oromucosal sprays.

Nearly 10% of cannabis users report using it for medicinal purposes.

Associated with decreased educational level, impaired workplace productivity, increased risk of use of other substances, adversely effects respiratory and cardiovascular systems and plays a major role in motor vehicle accidents.

Has a much less affect on motor skills than alcohol.

It is recommended that if cannabis is ingested, no driving for eight hours, if it is used transmucosally, no driving for four hours, and if inhaled no driving for two hours.

Evidence exists for its use to reduce nausea and vomiting during chemotherapy, reversing AIDS-related wasting and holds promise as an anti-spasmodic and analgesic agent.

Abuse and dependence increases the risk of mood, anxiety and personality disorders.

Cannabis use peaks in young adulthood and decreases as young people enter relationships, marry, have children, advance their education, and enter into the workforce.

Use in the adult population has remained stable from 1991-2001.

Increase among young black and Hispanic women from 1991 to 2001.

Rates of abuse and dependence, as opposed to overall use, has increased from 18% in 1991 to 30.2% by 2001.

Potency of delta-9-tetrahydrocannabinolhas increased by 66% from 1992 to 2002, accounting for greater addiction potential from 1991 to 2001.

Frequency of use unchanged from 1991 to 2001.

Increasing use by younger people associated with a greater risk of abuse and dependence.

Prevalence among college users has increased to 30%.

Majority of users or abusers are young individuals.

Increases in use by adult men and women ages 45-64 years.

Following inhalation by smoking effects occur in 10 to 20 minutes and last 2-3 hours.

Joints contain about 500 mg of marijuana, with approximately 5-15 mg of tetrahydrocannabinol with a half-life of seven days.

Produces mild euphoria followed by sleepiness.

In the acute state there is altered time perception, inhibition of emotions, psycho motor dysfunction, impaired immediate memory and conjunctival injection.

Acute cannabis use affects jjudgment.

In high doses psychmimetic effects occur.

May aggravate existing mental illness and impair motor performance.

Chronic use is associated with an increased risk of psychiatric illness and addiction.

Daily use of more than one 8th ounce of cannabis per week is associated with worsening functional status, including lower income, greater need for Socio economic assistance, criminal behavior, unemployment, and decreased life satisfaction (Volkow ND).

A significant association exists between cannabis use and the development of psychotic disorders, such as schizophrenia, particularly among heavy users.

With prolonged use laryngitis and rhinitis and chronic obstructive pulmonary disease may occur.

Abrupt withdrawal may cause similar symptoms to opioid withdrawal in habitual users.

Not associated with chronic cardiac disease.

Associated with respiratory damage, cardiovascular disease, impaired cognitive development, and mental illness.

Adverse cognitive defects include: impaired memory, impaired motor coordination, altered judgment, and in high doses, paranoia and psychosis.

Long-term use may depress testosterone levels and reduce sperm counts in men.

Long-term use on a daily basis is associated with poorer verbal memory in middle age than to peers who have not smoked marijuana habitually (Auer A).

Individuals with the greatest cumulative exposure to marijuana have the poorest verbal memory, processing speed, and executive functioning.

Case control studies have found generally poorer verbal learning, memory, and attention in patients who regularly use marijuana than in controls.

May be associated with abnormal menstrual pattern and failure to ovulate in some women.

Commonly associated with cognitive impairment.

Impaired cognitive function is an acute event of marijuana use.

Increasing evidence that impaired cognitive function may persist in life.

Heavy and long-term use is associated with cognitive impairment, particularly in learning and remembering new information.

In a study the Coronary ARTERY Risk Development Young Adults (CARDIA) study, a cohort of 5115 men and women followed for 25 years with exposure to marijuana.:

Past exposure to marijuana was associated with worse verbal memory but did not appear to affect other domains of cognitive function (Aier R et al).

Withdrawal may produce nausea, my allergies, irritability, and insomnia.

Children who use marijuana have about a four times increased likelihood of becoming adults with chronic and heavy use.

Marijuana smoke has many of the same constituents as tobaccos smoke.

Marijuana smokers have evidence of mucosal injury and inflammation of airways, respiratory symptoms such as cough, sputum production, and wheeze similar to tobacco smokers.

Occasional and low use is not associated with adverse pulmonary function (Pletcher MJ et al).

In its current form smoke marijuana is less deadly than tobacco.

Regular smokers of marijuana appear to be at greater risk for lung damage than people who smoke tobacco alone.

Emphysema was significantly more common among marijuana smokers (75%) than nonsmokers (5%). 

When matched for age and sex, 93% of marijuana smokers had emphysema, vs 67% of those who smoked tobacco only.

Marijuana smokers may develop lung damage earlier or with less exposure.

Marijuana smokers have higher rates of airway inflammation, the researchers found.

Most marijuana smokers also smoke cigarettes: whether the observed damage is caused by marijuana alone or occurred in combination with tobacco is impossible to determine.

Case studies have found increased mortality associated with heavy marijuana use attributable to vehicle accidents, suicide, respiratory cancers and brain cancers (Calabria B et al).

About 9% of users meet the criteria for dependence at sometime in their lives, as compared with 32% of tobacco users.

The concentration of the principal psychoactive, tetrahydrocannibal, constituent has more than doubled over the last 40 years.

New delivery systems, via a vaporizer, may decrease lung irritation, but may increase consumption enabling more and deeper inhalations.

Meta-analysis of cannabinoids for medical use of 79 studies:moderate evidence supports use for chronic pain and spasticity, low quality evidence in reducing nausea and vomiting due to chemotherapy, weight gain in HIV, sleep disorders, and Tourette syndrome (whiting P et al.).

Use in Parkinson’s disease, posttraumatic stress disorder, and Tourette�s syndrome have a hypothetical rationale but weak clinical evidence of benefit.

Cannabinoids for medical use associated with dizziness, dry mouth, fatigue, nausea, somnolence , vomiting, confusion, impaired balance, disorientation, and hallucinations.

Overall clinical research supports medical marijuana use in alleviating chronic neuropathic or cancer pain, spasticity, nausea, vomiting, weight loss, wasting syndrome associated with chronic debilitating processes, glaucoma and potential reduction in opioid use with it with analgesic enhancement n analgesic abuse.

Acute use associated with impaired learning, memory, attention, and motor coordination that can affect important activities of daily living, such as driving.

Possible efficacy of marijuana use is suggested in fibromyalgia, posttraumatic stress disorder, seizure disorders, irritable bowel syndrome, and Crohn’s disease.

Contraindications to use include personal or family history of psychoses, age younger than 18 years, and pregnancy or breast-feeding.

The prevalence of marijuana use among pregnant women is approximately 7%.

The use of marijuana in pregnancy is associated with a significant increase in the rate of preterm birth.

Cannabis use is associated with a 12% preterm birth rate, while it is is 6.1% among non-users.

In a  multi center observational study adverse pregnancy outcome-small for gestational age birth, medically indicated preterm birth, stillbirth, or hypertensive disorder in pregnancy are more frequent in patients with cannabis exposure.

The risk for adverse outcomes is higher among those who continue to use cannabis beyond the first trimester.

Cannabis you should be avoided during pregnancy to optimize, maternal and neonatal outcomes.

Marketing of marijuana to pregnant women for morning sickness is occurring despite accumulating evidence of harm.

Cannabinoids can cross the placenta and into the fetal bloodstream.

Medical marijuana users are unlikely to develop pulmonary or immune effects, cognitive impairment that persist beyond acute dose or the development of the psychotic disorder when appropriately screened.

Lifetime addiction prevalence 1.5%-9% in recreational users.

Likelihood of prevalence of addiction in medical users is unknown.

Medical marijuana use is not indicated for first-line therapy for any process, instead its greatest therapeutic potential is treating patients with chronic conditions refractory to standard therapy.

Cancer patients receiving cannabinoids compared to patients without cannabinoids had a higher symptom severity score for pain, nausea, appetite, spiritual well-being, and insomnia (Chang YD).

Active cannabis use is not associated with markers of inflammation such as C reactive proteins, fibrinogen, or interleukin 6.

Lifetime cannabis is inversely associated with fibrinogen levels.

There are no effective pharmacological interventions for cannabinoid addiction.

Following the legalization of cannabis in British Columbia, the prevalence of moderately injured drivers with a THC level of at least 2 ng/mL in trauma centers more than doubled: largest increases in males and older drivers.

Acute psychological effects include: euphoria, relaxation, sedation, increased, appetite (munchies), impaired short term memory, concentration, and psychomotor coordination.

Some individuals experience anxiety, panic attacks, paranoia, especially at high doses. 

Psychotic symptoms are less common. 

Acute physical effects include impaired motor coordination, slurred speech, dry mouth, conjunctival, irritation and redness, tachycardia, orthostatic, hypotension, and horizontal nystagmus.

Smoked cannabis can induce cough, wheezing, dyspnea, increased sputum production, and exacerbate asthma. 

Cannabis can be associated with acute transient, cardiac arrhythmia, including atrial fibrillation, supraventricular tachycardia, PVCs, and sustained ventricular tachycardia.