EFFECTS OF CANNABIS – A REVIEW

Inter. J. of Phytotherapy / Vol 3 / Issue 1 / 2013 / 24-32.

~ 24 ~

e - ISSN - 2249-7722

Print ISSN - 2249-7730

International Journal of Phytotherapy

www.phytotherapyjournal.com

EFFECTS OF CANNABIS A REVIEW

G. Sangeetha, G. Balammal*, K. Umasankar

*Krishna Teja Pharmacy College, Chadalawada Nagar, Renigunta Road, Tirupati-517605, Andhra Pradesh, India.

INTRODUCTION

Cannabinoids and cannabinoid receptors

The most prevalent psychoactive substances

in cannabis are cannabinoids, most notably THC. Some

varieties, having undergone careful selection and growing

techniques, can yield as much as 29% THC. Another

psychoactive cannabinoid present in Cannabis

sativa is tetrahydrocannabivarin (THCV), but it is only

found in small amounts and is a cannabinoid antagonist.

In addition, there are also similar compounds

contained in cannabis that do not exhibit any psychoactive

response but are obligatory for functionality cannabidiol

(CBD), an isomer of THC; cannabinol (CBN),

an oxidation product of THC; cannabivarin (CBV),

an analog of CBN with a

different sidechain cannabidivarin (CBDV), an analog

of CBD with a different side chain, and cannabinolic acid.

How these other compounds interact with THC is not

fully understood. Some clinical studies have proposed that

CBD acts as a balancing force to regulate the strength of

the psychoactive agent THC. CBD is also believed to

regulate the bodys metabolism of THC by inactivating cytochrome P450, an important class o f

enzymes that metabolize drugs. Experiments in which

mice were treated with CBD followed by THC showed

that CBD treatment was associated with a substantial

increase in brain concentrations of THC and its major

metabolites, most likely because it decreased the rate of

clearance of THC from the body. Cannabis cofactor

compounds have also been linked to lowering body

temperature, modulating immune functioning, and cell

protection. The essential oil of cannabis contains many

fragrant terpenoids which may synergize with the

cannabinoids to produce their unique effects. THC is

converted rapidly to 11-hydroxy-THC, which is also

pharmacologically active, so the drug effect outlasts

measurable THC levels in blood.

THC and cannabidiol are

also neuroprotective antioxidants. Research in rats has

indicated that THC prevented hydroperoxide-

induced oxidative damage as well as or better than other

antioxidants in a chemical (Fenton reaction) system

and neuronal cultures. Cannabidiol was significantly more

protective than either vitamin E or vitamin C.

Corresponding Author:- G. Balammal Email: [email protected]

ABSTRACT

The effects of cannabis are caused by chemical compounds in cannabis, including cannabinoids such

as tetrahydrocannabinol (THC). Cannabis has both psychologicaland physiological effects on the human body.

Acute effects while under the influence can include euphoria and anxiety. This review Concerns the potential effect

for long-term cannabis consumption to increase risk for schizophrenia, bipolar disorders, and major depression, but

the ultimate conclusions on these factors are disputed. The evidence of long-term effects on memory is preliminary

and hindered by confounding factors. For thousands of years people have believed that cannabis has religious and

spiritual effects.

Key words: Cannabis, Physiological effects, Long-term consumption.


~ 25 ~

The cannabinoid receptor is a typical member of

the largest known family of receptors called a G protein-

coupled receptor. A signature of this type of receptor is

the distinct pattern of how the receptor molecule spans

the cell membrane seven times. The location of

cannabinoid receptors exists on the cell membrane, and

both outside (extracellularly) and inside (intracellularly)

the cell membrane. CB1 receptors, the bigger of the two,

are extraordinarily abundant in the brain: 10 times more

plentiful than -opioid receptors, the receptors responsible for the effects of morphine. CB2 receptors are structurally

different (the sequence similarity between the two

subtypes of receptors is 44%), found only on cells of the

immune system, and seems to function similarly to its

CB1 counterpart. CB2 receptors are most commonly

prevalent on B-cells, natural killer cells, and monocytes,

but can also be found on polymorphonuclear neutrophil

cells, T8 cells, and T4 cells. In the tonsils the CB2

receptors appear to be restricted to B-lymphocyte-

enriched areas [1,2].

Biochemical mechanisms in the brain

In 1990 the discovery of cannabinoid

receptors located throughout the brain and body, along

with endogenous cannabinoid neurotransmitters like anan

damide (a lipidmaterial derived ligand from arachidonic

acid), suggested that the use of cannabis affects the brain

in the same manner as a naturally occurring brain

chemical.Cannabinoids usually contain a 1,1'-di-methyl-

pyrane ring, a variedly derivatized aromatic ring and a

variedly unsaturated cyclohexyl ring and their immediate

chemical precursors, constituting a family of about 60 bi-

cyclic and tri-cyclic compounds. Like most other

neurological processes, the effects of cannabis on the

brain follow the standard protocol of signal transduction,

the electrochemical system of sending signals

through neurons for a biological response. It is now

understood that cannabinoid receptors appear in similar

forms in most vertebrates and invertebrates and have a

long evolutionary history of 500 million years. The

binding of cannabinoids to cannabinoid receptors

decrease adenylyl cyclase activity, inhibit calcium N

channels, and disinhibit K+

A channels. There are two

types of cannabinoid receptors (CB1 and CB2) [3].

The CB1 receptor is found primarily in the brain

and mediates the psychological effects of THC. The CB2

receptor is most abundantly found on cells of the immune

system. Cannabinoids act as immunomodulators at CB2

receptors, meaning they increase some immune responses

and decrease others. For example, nonpsychotropic

cannabinoids can be used as a very effective anti-

inflammatory. The affinity of cannabinoids to bind to

either receptor is about the same, with only a slight

increase observed with the plant-derived compound CBD

binding to CB2 receptors more frequently. Cannabinoids

likely have a role in the brains control of movement and memory, as well as natural pain

modulation. It is clear that cannabinoids can affect pain

transmission and, specifically, that cannabinoids interact

with the brain's endogenous opioid system and may affect

dopamine transmission. This is an important

physiological pathway for the medical treatment of pain.

Sustainability in the body

Most cannabinoids are lipophilic (fat soluble)

compounds that are easily stored in fat, thus yielding a

long elimination half-life relative to other recreational

drugs. The THC molecule, and related compounds, are

usually detectable in drug tests from 3 days up to 10 days

according to Redwood Laboratories; heavy users can

produce positive tests for up to 3 months after ceasing

cannabis use.

Toxicity

THC, the principal psychoactive constituent of

the cannabis plant, has an extremely low toxicity and the

amount that can enter the body through the consumption

of cannabis plants poses no threat of death. In lab animal

tests, scientists have had much difficulty administering a

dosage of THC that is high enough to be lethal.

Accordingly, there is little reason to believe a human

would self-administer such doses. According to the Merck

Index, the LD50 of THC (the dose which causes the death

of 50% of individuals) is 1270 mg/kg for male rats and

730 mg/kg for female rats from oral consumption in

sesame oil, and 42 mg/kg for rats from inhalation.

The ratio of cannabis material required to

produce a fatal overdose to the amount required to

saturate cannabinoid receptors and cause intoxication is

approximately 40,000:1. A typical marijuana joint

contains less than 10 mg of THC, and one would have to

smoke thousands of those in a short period of time to

approach toxic levels. According to a 2006 United

Kingdom government report, using cannabis is much less

dangerous than tobacco, prescription drugs, and alcohol in

social harms, physical harm, and addiction. It was found

in 2007 that while tobacco and cannabis smoke are quite

similar, cannabis smoke contained higher amounts

ofammonia, hydrogen cyanide, and nitrogen oxides, but

lower levels of carcinogenic polycyclic aromatic

hydrocarbons (PAHs). This study found that directly

inhaled cannabis smoke contained as much as 20 times as

much ammonia and 5 times as much hydrogen cyanide as

tobacco smoke and compared the properties of both

mainstream and sidestream (smoke emitted from a

smouldering 'joint' or 'cone') smoke. Mainstream cannabis

smoke was found to contain higher concentrations of

selected polycyclic aromatic hydrocarbons (PAHs) than

sidestream tobacco smoke. However, other studies have

found much lower disparities in ammonia and hydrogen


~ 26 ~

cyanide between cannabis and tobacco, and that some

other constituents (such as polonium-210, lead, arsenic,

nicotine, and tobacco-specific nitrosamines) are either

lower or non-existent in cannabis smoke [4,5].

Cannabis smoke contains thousands of organic

and inorganic chemical compounds. This tar is chemically

similar to that found in tobacco smoke or cigars. Over

fifty known carcinogens have been identified in cannabis

smoke. These include nitrosamines, reactive aldehydes,

and polycylic hydrocarbons, including

benz[a]pyrene. Marijuana smoke was listed as a cancer

agent in California in 2009. A study by the British Lung

Foundation published in 2012 identifies cannabis smoke

as a carcinogen and also finds awareness of the danger is

low compared with the high awareness of the dangers of

smoking tobacco particularly among younger users. Other

observations include possible increased risk from each

cigarette; lack of research on the effect of cannabis smoke

alone; low rate of addiction compared to tobacco; and

episodic nature of cannabis use compared to steady

frequent smoking of tobacco.

Researches points out that the study cited by the

British Lung Foundation has been accused of both false

reasoning and incorrect methodology. Further, he notes

that other studies have failed to connect cannabis with

lung cancer, and accuses the BLF of scaremongering over

cannabis.

A study in the academic journal, Cancer

Epidemiology, Biomarkers & Prevention, demonstrated

that a marijuana cigarette deposits four times the amount

of tar in the human respiratory tract than a tobacco

cigarette.

According to Harvard's Lester Grinspoon, there

has never been a death associated directly to cannabis. In

defense of smoked Medical cannabis, Grinspoon noted,

there is very little evidence that smoking marijuana as a

means of taking it represents a significant health risk.

Although cannabis has been smoked widely in Western

countries for more than four decades, there have been no

reported cases of lung cancer or emphysema attributed to

marijuana. I suspect that a day's breathing in any city with

poor air quality poses more of a threat than inhaling a

day's dose -- which for many ailments is just a portion of

a joint of marijuana.

One study in 2005, the largest of its kind, found

no cannabis-cancer connection. Donald Tashkin,

a pulmonologist at UCLA's David Geffin School of

Medicine who studied marijuana for 30 years, noted: We

hypothesized that there would be a positive association

between marijuana use and lung cancer, and that the

association would be more positive with heavier use.

What we found instead was no association at all, and even

a suggestion of some protective effect.

Short-term effects

When smoked, the short-term effects of cannabis

manifest within seconds and are fully apparent within a

few minutes, typically lasting for 1-3 hours, varying by

the person and the strain of marijuana. The duration of

noticeable effects has been observed to diminish due to

prolonged, repeated use and the development of a

tolerance to cannabinoids.

Psychoactive effects

The psychoactive effects of cannabis, known as a

high, are subjective and can vary based on the person and

the method of use.

When THC enters the blood stream and reaches the

brain, it binds to cannabinoid receptors. The endogenous

ligand of these receptors is anandamide, the effects of

which THC emulates. This agonism of the cannabinoid

receptors results in changes in the levels of various

neurotransmitters,

especially dopamine and norepinephrine;

neurotransmitters which are closely associated with the

acute effects of cannabis ingestion, such

as euphoria and anxiety. Some effects may include a

general alteration of conscious perception, euphoria,

feelings of well-being, relaxation or stress reduction,

increased appreciation of humor, music (especially

discerning its various components/instruments) or the

arts, joviality, metacognition and introspection, enhanced

recollection (episodic memory), increased sensuality,

increased awareness of sensation, increased libido, and

creativity. Abstract or philosophical thinking, disruption

of linear memory and paranoia or anxiety are also

typical. Anxiety is the most commonly reported side

effect of smoking marijuana. Between 20 and 30 percent

of recreational users experience intense anxiety

and/or panic attacks after smoking cannabis.

Cannabis also produces many subjective and

highly tangible effects, such as greater enjoyment of food

taste and aroma, an enhanced enjoyment of music and

comedy, and marked distortions in theperception of

time and space (where experiencing a rush of ideas from

the bank of long-term memory can create the subjective

impression of long elapsed time, while a clock reveals

that only a short time has passed). At higher doses, effects

can include altered body image, auditory and/or visual

illusions, pseudo-hallucinatory or (rarely, at very high

doses) fully hallucinatory experiences, and ataxia from

selective impairment of polysynaptic reflexes. In some

cases, cannabis can lead to dissociative states such

as depersonalization and derealization; such effects are

most often considered desirable, but have the potential to

induce panic attacks and paranoia in some unaccustomed

users [3].

Somatic effects

Some of the short-term physical effects of

cannabis use include increased heart rate, dry mouth,


~ 27 ~

reddening of the eyes (congestion of

the conjunctival blood vessels), a reduction in intra-ocular

pressure, muscle relaxation and a sensation of cold or hot

hands and feet.

Electroencephalography or EEG shows

somewhat more persistent alpha waves of slightly

lower frequency than usual. Cannabinoids produce a

marked depression of motor activity via activation of

neuronal cannabinoid receptors belonging to the CB1

subtype.

Duration

Effects of cannabis generally range from 10

minutes to 8 hours, depending on the potency of the dose,

other drugs consumed, route of administration, set,

setting, and personal tolerance to the drug's various

effects.

Smoked

The total short-term duration of cannabis use

when smoked is based on the potency and how much is

smoked. Effects can typically last two to three hours.

A study of ten healthy, robust, male volunteers

who resided in a residential research facility sought to

examine both acute and residual subjective, physiologic,

and performance effects of smoking marijuana cigarettes.

On three separate days, subjects smoked

one NIDA marijuana cigarette containing either 0%,

1.8%, or 3.6% THC, documenting subjective,

physiologic, and performance measures prior to smoking,

five times following smoking on that day, and three times

on the following morning. Subjects reported robust

subjective effects following both active doses of

marijuana, which returned to baseline levels within 3.5

hours. Heart rate increased and the pupillary light

reflex decreased following active dose administration

with return to baseline on that day. Additionally,

marijuana smoking acutely produced decrements

in smooth pursuit eye tracking. Although robust acute

effects of marijuana were found on subjective and

physiological measures, no effects were evident the day

following administration, indicating that the residual

effects of smoking a single marijuana cigarette are

minimal [4].

A Dutch double blind, randomized, placebo-

controlled, cross-over study examining male volunteers

aged 1845 years with a self-reported history of regular cannabis use concluded that smoking of cannabis with

very high THC levels (marijuana with 923% THC), as currently sold in coffee shops in the Netherlands, may

lead to higher THC blood-serum concentrations. This is

reflected by an increase of the occurrence of impaired

psychomotor skills, particularly among younger or

inexperienced cannabis smokers, who do not always adapt

their smoking-style to the higher THC content. High THC

concentrations in cannabis were associated with a dose-

related increase of physical effects (such as increase of

heart rate, and decrease of blood pressure) and

psychomotor effects (such as reacting more slowly,

decreased ability to focus and concentrate, making more

mistakes during performance testing, having less motor

control, and experiencing drowsiness). It was also

observed during the study that the effects from a

single joint lasted for more than eight hours. Reaction

times remained impaired five hours after smoking, when

the THC serum concentrations were significantly reduced,

but still present. However, it is important to note that the

subjects (without knowing the potency) were told to finish

their (unshared) joints rather than titrate their doses,

leading in many cases to significantly higher doses than

they would normally take. Also, when subjects smoke on

several occasions per day, accumulation of THC in blood-

serum may occur [5].

Oral

When taken orally (in the form of capsules, food

or drink), the psychoactive effects take longer to manifest

and generally last longer, typically lasting for 410 hours after consumption. Very high doses may last even longer.

Also, oral ingestion use eliminates the need to inhale toxic

combustion products created by smoking and therefore

reduces the risk of respiratory harm associated with

cannabis smoking [6].

Neurological effects

The areas of the brain where cannabinoid

receptors are most prevalently located are consistent with

the behavioral effects produced by cannabinoids. Brain

regions in which cannabinoid receptors are very abundant

are the basal ganglia, associated with movement control;

the cerebellum, associated with body movement

coordination; the hippocampus, associated with learning,

memory, and stress control; thecerebral cortex, associated

with higher cognitive functions; and the nucleus

accumbens, regarded as the reward center of the brain.

Other regions where cannabinoid receptors are

moderately concentrated are the hypothalamus, which

regulates homeostatic functions; the amygdala, associated

with emotional responses and fears; the spinal cord,

associated with peripheral sensations like pain; the brain

stem, associated with sleep, arousal, and motor control;

and the nucleus of the solitary tract, associated with

visceral sensations like nausea and vomiting.

Most notably, the two areas of motor control and

memory are where the effects of cannabis are directly and

irrefutably evident. Cannabinoids, depending on the dose,

inhibit the transmission of neural signals through the basal

ganglia and cerebellum. At lower doses, cannabinoids

seem to stimulate locomotion while greater doses inhibit

it, most commonly manifested by lack of steadiness (body

sway and hand steadiness) in motor tasks that require a lot

of attention. Other brain regions, like the cortex, the


~ 28 ~

cerebellum, and the neural pathway from cortex

to striatum, are also involved in the control of movement

and contain abundant cannabinoid receptors, indicating

their possible involvement as well.

Experiments on animal and human tissue have

demonstrated a disruption of short-term

memory formation, which is consistent with the

abundance of CB1 receptors on the hippocampus, the

region of the brain most closely associated with memory.

Cannabinoids inhibit the release of several

neurotransmitters in the hippocampus such

as acetylcholine, norepinephrine, and glutamate, resulting

in a major decrease in neuronal activity in that region.

This decrease in activity resembles a temporary

hippocampal lesion.

In in-vitro experiments THC at extremely high

concentrations, which could not be reached with

commonly consumed doses, caused competitive

inhibition of the AChE enzyme and inhibition of -amyloidpeptide aggregation, implicated in the

development of Alzheimer's disease. Compared to

currently approved drugs prescribed for the treatment of

Alzheimer's disease, THC is a considerably superior

inhibitor of aggregation, and this study provides a

previously unrecognized molecular mechanism through

which cannabinoid molecules may impact the progression

of this debilitating disease [6].

Effects on driving

Cannabis usage has been shown to have a

negative effect on driving ability.[54]

The British Medical

Journal indicated that drivers who consume cannabis

within three hours of driving are nearly twice as likely to

cause a vehicle collision as those who are not under the

influence of drugs or alcohol [7].

In Cannabis and driving: a review of the

literature and commentary, the United

Kingdom's Department for Transport reviewed data on

cannabis and driving, finding Cannabis impairs driving

behaviour. However, this impairment is mediated in that

subjects under cannabis treatment appear to perceive that

they are indeed impaired. Where they can compensate,

they do, for example ... effects of driving behaviour are

present up to an hour after smoking but do not continue

for extended periods. The report summarizes current

knowledge about the effects of cannabis on driving and

accident risk based on a review of available literature

published since 1994 and the effects of cannabis on

laboratory based tasks. The study identified young males,

amongst whom cannabis consumption is frequent and

increasing, and in whom alcohol consumption is also

common, as a risk group for traffic accidents. The cause,

according to the report, is driving inexperience and

factors associated with youth relating to risk taking,

delinquency and motivation. These demographic and

psychosocial variables may relate to both drug use and

accident risk, thereby presenting an artificial relationship

between use of drugs and accident involvement [8].

Kelly, Darke and Ross show similar results, with

laboratory studies examining the effects of cannabis on

skills utilised while driving showing impairments in

tracking, attention, reaction time, short-term memory,

hand-eye coordination, vigilance, time and distance

perception, and decision making and concentration. An

EMCDDA review concluded that the acute effect of

moderate or higher doses of cannabis impairs the skills

related to safe driving and injury risk, specifically

attention, tracking and psychomotor skills. In their review

of driving simulator studies, Kelly et al. conclude that

there is evidence of dose-dependent impairments in

cannabis-affected drivers' ability to control a vehicle in

the areas of steering, headway control, speed variability,

car following, reaction time and lane positioning. The

researchers note that even in those who learn to

compensate for a drug's impairing effects, substantial

impairment in performance can still be observed under

conditions of general task performance (i.e. when no

contingencies are present to maintain compensated

performance).

A report from the University of

Colorado, Montana State University, and the University

of Oregon found that on average, states that have

legalized Medical cannabis had a decrease in traffic-

related fatalities by 8-11%. Drunk drivers take more risk,

they tend to go faster. They dont realize how impaired they are. People who are under the influence of marijuana

drive slower, they dont take as many risks. Another consideration, they added, was the fact that users of

marijuana tend not to go out as much [9].

Cardiovascular effects

Cannabis arteritis is a very rare peripheral

vascular disease similar to Buerger's disease. There were

about 50 confirmed cases from 1960 to 2008, all of which

occurred in Europe. However, all of the cases also

involved tobacco (a known cause of Buerger's disease) in

one way or another, and nearly all of the cannabis use was

quite heavy. In Europe, cannabis is typically mixed with

tobacco, in contrast to North America.

A 2008 study by the National Institutes of

Health Biomedical Research Centre in Baltimore found

that heavy, chronic smoking of marijuana (138 joints per

week) changed blood proteins associated with heart

disease and stroke. This may be a result of raised

carboxyhemoglobin levels from carbon monoxide. A

similar increase in heart disease and ischemic strokes is

observed in tobacco smokers, which suggests that the

harmful effects come from a variety of combustion

products, not just marijuana.

A 2005 article in the Journal of Neurology,

Neurosurgery and Psychiatry reported on a 36-year-old

man who suffered a stroke on three separate occasions


~ 29 ~

after smoking a large amount of marijuana, despite having

no known risk factors for the disorder, suggesting that a

rare side effect of marijuana use may be an increase in the

incidence of strokes among young smokers. A 2000 study

by researchers at Boston's Beth Israel Deaconess Medical

Center, Massachusetts General Hospital and Harvard

School of Public Health also found that a middle-age

person's risk of heart attack rises nearly fivefold in the

first hour after smoking marijuana, about twice the risk as

vigorous exercise or sexual intercourse [10].

Adulterated cannabis

Contaminants may be found in hashish obtained

from soap bar-type sources. The dried flowers of the plant

may be contaminated by the plant taking up heavy metals

and other toxins from its growing environment, or by the

addition of lead or glass beads, used to increase the

weight or to make the cannabis appear as if it has more

crystal-looking trichomes indicating a higher THC

content. Users who burn hot or mix cannabis with tobacco

are at risk of failing to detect deviations from appropriate

cannabis taste.

Despite cannabis being generally perceived as a

natural or chemical-free product, in a recent Australian

survey one in four Australians consider cannabis grown

indoors under hydroponic conditions to be a greater health

risk due to increased contamination, added to the plant

during cultivation to enhance the plant growth and quality

[11].

Combination with other drugs

The most obvious confounding factor in

cannabis research is the prevalent usage of other

recreational drugs, especially alcohol and nicotine. Such

complications demonstrate the need for studies on

cannabis that have stronger controls, and investigations

into alleged symptoms of cannabis use that may also be

caused by tobacco. Some critics question whether

agencies doing the research make an honest effort to

present an accurate, unbiased summary of the evidence, or

whether they cherry-pick their data to please funding

sources which may include the tobacco industry or

governments dependent on cigarette tax revenue; others

caution that the raw data, and not the final conclusions,

are what should be examined.

Cannabis also has been shown to have a

synergistic cytotoxic effect on lung cancer cell cultures in

vitro with the food additive butylated

hydroxyanisole (BHA) and possibly the related

compound butylated hydroxytoluene (BHT). The study

concluded, Exposure to marijuana smoke in conjunction

with BHA, a common food additive, may promote

deleterious health effects in the lung. BHA & BHT are

human-made fat preservatives, and are found in many

packaged foods including: plastics in boxed cereal, Jello,

Slim Jims, and more.

The Australian National Household Survey of

2001 showed that cannabis use in Australia is rarely used

without other drugs. 95% of cannabis users also drank

alcohol; 26% took amphetamines; 19% took ecstasy and

only 2.7% reported not having used any other drug with

cannabis. While research has been undertaken on the

combined effects of alcohol and cannabis on performing

certain tasks, little research has been conducted on the

reasons why this combination is so popular. Evidence

from a controlled experimental study undertaken by

Lukas and Orozco suggests that alcohol causes THC to be

absorbed more rapidly into the blood plasma of the user.

Data from the Australian National Survey of Mental

Health and Wellbeing found that three-quarters of recent

cannabis users reported using alcohol when cannabis was

not available [12].

Memory and learning

Studies on cannabis and memory are hindered by

small sample sizes, confounding drug use, and other

factors. The strongest evidence regarding cannabis and

memory focuses on its temporary negative effects on

short-term and working memory.

In a 2001 study looking at neuropsychological

performance in long-term cannabis users, researchers

found some cognitive deficits appear detectable at least 7

days after heavy cannabis use but appear reversible and

related to recent cannabis exposure rather than

irreversible and related to cumulative lifetime use. On his

studies regarding cannabis use, lead researcher and

Harvard professor Harrison Pope said he found marijuana

is not dangerous over the long term, but there are short-

term effects. From neuropsychological tests, Pope found

that chronic cannabis users showed difficulties, with

verbal memory in particular, for at least a week or two

after they stopped smoking. Within 28 days, memory

problems vanished and the subjects were no longer

distinguishable from the comparison group.

Researchers from the University of California,

San Diego School of Medicine failed to show substantial,

systemic neurological effects from long-term recreational

use of cannabis. Their findings were published in the July

2003 issue of the Journal of the International

Neuropsychological Society. The research team, headed

by Dr Igor Grant, found that cannabis use did affect

perception, but did not cause permanent brain damage.

Researchers looked at data from 15 previously published

controlled studies involving 704 long-term cannabis users

and 484 nonusers. The results showed long-term cannabis

use was only marginally harmful on the memory and

learning. Other functions such as reaction time, attention,

language, reasoning ability, perceptual and motor skills

were unaffected. The observed effects on memory and

learning, they said, showed long-term cannabis use

caused selective memory defects, but that the impact was

of a very small magnitude.


~ 30 ~

Appetite

The feeling of increased appetite following the

use of cannabis has been documented for hundreds of

years, and is known as the munchies in popular culture.

Clinical studies and survey data have found that cannabis

increases food enjoyment and interest in food. Scientists

have claimed to be able to explain what causes the

increase in appetite, concluding that endocannabinoids in

the hypothalamus activate cannabinoid receptors that are

responsible for maintaining food intake. Rarely, chronic

users experience a severe vomiting disorder, cannabinoid

hyperemesis syndrome, after smoking and find relief by

taking hot baths.

Endogenous cannabinoids (endocannabinoids)

were discovered in cow's milk and soft

cheeses. Endocannabinoids were also found in human

breast milk. It is widely accepted that the neonatal

survival of many species is largely dependent upon their

suckling behavior, or appetite for breast milk and recent

research has identified the endogenous cannabinoid

system to be the first neural system to display complete

control over milk ingestion and neonatal survival. It is

possible that cannabinoid receptors in our body interact

with the cannabinoids in milk to stimulate a suckling

response in newborns so as to prevent growth failure [13].

Long-Term Effects

Though the long-term effects of cannabis have

been studied, there remains much to be concluded;

debated topics include the drug's addictiveness, its

potential as a gateway drug, its effects on intelligence and

memory, and its contributions to mental disorders such as

schizophrenia and depression. On some such topics, such

as the drug's effects on the lungs, relatively little research

has been conducted, leading to division as to the severity

of its impact. However, a study funded by the US

government on the long term lung-related effects of

marijuana has concluded that moderate marijuana use

does not impair pulmonary function.

More research is no guarantee of greater

consensus in the field of cannabis studies, however; both

advocates and opponents of the drug are able to call upon

multiple scientific studies supporting their respective

positions. Cannabis has been correlated with the

development of various mental disorders in multiple

studies, for example a recent 10 year study on 1,923

individuals from the general population inGermany, aged

1424, concluded that cannabis use is a risk factor for the development of incident psychotic symptoms. Continued

cannabis use might increase the risk for psychotic

disorder.

Efforts to prove the gateway drug hypothesis that

cannabis and alcohol makes users more inclined to

become addicted to harder drugs like cocaine and heroin

have produced mixed results, with different studies

finding varying degrees of correlation between the use of

cannabis and other drugs, and some finding none.

However, believe the gateway effect, currently being

pinned on the use of marijuana, should not be attributed to

the drug itself but rather the illegality of the drug in most

countries. Supporters of this theory believe that the

grouping of marijuana and harder drugs in law is, in fact,

the cause of users of marijuana to move on to those harder

drugs.

There have been debates as to whether cannabis

can lead to heavy addiction. According to one of the

studies on the issue, the La Guardia Committee of 1944,

smoking marijuana could help to get out of the addiction

from substances like cocaine or morphine.

Cannabis withdrawal is included in the proposed

revision of DSM-5. Several drugs have been investigated

in an attempt to ameliorate the symptoms of cannabis

withdrawal. Such drugs include bupropion

, divalproex, nefazodone, lofexidine,and dronabinol. Of

these, dronabinol has proven the most effective.

Effects In Pregnancy

A study of 600 mothers that reported smoking

cannabis during pregnancy suggested that it was not

associated with increased risk of perinatal

mortality. However, frequent and regular use of cannabis

throughout pregnancy may be associated with a small but

statistically detectable decrease in birth weight.

Melanie Dreher, dean of nursing at Rush

Medical Center in Chicago, conducted a study of

Jamaican women who used cannabis throughout their

pregnancies, as well as their babies' first year. The study

was published in the American Journal of Pediatrics in

1994. Dreher expected to see a decrease in birth weight,

but saw none. Instead, the exposed babies socialized and

made eye contact more quickly, had better organization

and modulation of sleeping and waking, and were less

prone to anxiety. On difference between the Jamaican and

other studies' results, Medicine hunter Chris

Kilham noted, In U.S. studies where we've seen a similar

investigation, women have concurrently been abusing

alcohol and other drugs as well [14].

Pathogens and microtoxins

Most microorganisms found in cannabis only

affect plants and not humans, but some microorganisms,

especially those that proliferate when the herb is not

correctly dried and stored, can be harmful to humans.

Some users may store marijuana in an airtight bag or jar

in a refrigerator to prevent fungal and bacterial growth

[15].

Fungi

The fungi Aspergillus flavus, Aspergillus

fumigatus, Aspergillus niger, Aspergillus

parasiticus, Aspergillus tamarii, Aspergillus

sulphureus, Aspergillus repens, Mucor


~ 31 ~

hiemalis, Penicillium chrysogenum, Penicillium

italicum and Rhizopus nigrans have been found in moldy

cannabis. Aspergillus mold species can infect the lungs

via smoking or handling of infected cannabis and cause

opportunistic and sometimes deadlyaspergillosis. Some of

the microorganisms found create aflatoxins, which

are toxic and carcinogenic. Researchers suggest that

moldy cannabis thus be discarded.

Mold is also found in smoke from mold infected

cannabis, and the lungs and nasal passages are a major

means of contracting fungal infections. Levitz and

Diamond (1991) suggested baking marijuana in home

ovens at 150 C [302 F], for five minutes before

smoking. Oven treatment killed conidia of A.

fumigatus, A. flavus and A. niger, and did not degrade the

active component of marijuana, tetrahydrocannabinol

(THC) [16].

Bacteria

Cannabis contaminated with Salmonella

muenchen was positively correlated with dozens of cases

of salmonellosis in 1981. Thermophilic actinomycetes

were also found in cannabis [17].

Fig 1. The structural formula of tetrahydrocannabinol

Fig 2. Tetrahydrocannabivarin

Fig 3. Cannabidiol

Fig 4. Cannabinol

Fig 5. Cannabivarin

Fig 6. Cannabidivarin

Fig 7. Aspergillus fumigatus


~ 32 ~

CONCLUSION

In many countries, experimental science regarding

cannabis is restricted due to its illegality. Thus, cannabis

as a drug is often hard to fit into the structural confines of

medical research because appropriate, research-grade

samples are difficult to obtain for research purposes,

unless granted under authority of national governments.

REFERENCES 1. Osborne Geraint B, Fogel Curtis. Understanding the Motivations for Recreational Marijuana Use among Adult

Canadians1. Substance Use & Misuse, 43(3-4), 2008, 539-72.

2. Ranganathan, Mohini, Dsouza Deepak Cyril. The acute effects of cannabinoids on memory in humans: a review. Psychopharmacology, 188(4), 2006, 425-44.

3. Leweke, F. Markus, Koethe Dagmar. Cannabis and psychiatric disorders: it is not only addiction. Addiction Biology, 13(2), 2008, 26475.

4. Rubino T, Parolaro D. Long lasting consequences of cannabis exposure in adolescence. Molecular and Cellular Endocrinology, 286(12 Suppl 1), 2008, S108-13.

5. Delisi, Lynn E. The effect of cannabis on the brain: can it cause brain anomalies that lead to increased risk for schizophrenia?. Current Opinion in Psychiatry, 21(2), 2008, 140-50.

6. Denson TF, Earleywine M. Decreased depression in marijuana users. Addictive behaviors, 31(4), 2006, 738-42. 7. Grotenhermen Franjo. The Toxicology of Cannabis and Cannabis Prohibition. Chemistry & Biodiversity, 4(8), 2007,

1744-69.

8. Riedel G, Davies SN. Cannabinoid Function in Learning, Memory and Plasticity. Handbook of Experimental Pharmacology, 168(168), 2005, 445-477.

9. Kalant HK & Roschlau WHE. Principles of Medical Pharmacology (6th ed.). 1998, p. 373-375. 10. Turner, Carlton E, Bouwsma Otis J, Billets Steve, Elsohly Mahmoud A. Constituents ofCannabis sativa L. XVIII

Electron voltage selected ion monitoring study of cannabinoids. Biological Mass Spectrometry, 7 (6), 1980, 24756. 11. Joy JE, Watson SJ and Benson JA. Marijuana and Medicine: Assessing The Science Base. Washington D.C: National

Academy of Sciences Press, 1999.

12. Hampson AJ, Grimaldi M, Axelrod J, Wink D. Cannabidiol and 9-tetrahydrocannabinol are neuroprotective antioxidants. Proceedings of the National Academy of Sciences, 95 (14), 1998, 826873.

13. Abadinsky H. Drugs: An Introduction (5th ed.). 2004, p. 62-77. 14. Moir David, Rickert William S, Levasseur Genevieve, Larose Yolande, Maertens Rebecca, White Paul, Desjardins

Suzanne. A Comparison of Mainstream and Sidestream Marijuana and Tobacco Cigarette Smoke Produced under Two

Machine Smoking Conditions. Chemical Research in Toxicology, 21(2), 2008, 494-502.

15. Marijuana VS. Tobacco smoke compositions, from: Institute of Medicine, Marijuana and Health, Washington, D.C. National Academy Press (Erowid.org), 1988.

16. Zuo-Feng Zhang, Hal Morgenstern, Margaret R. Spitz, Donald P. Tashkin, Guo-Pei Yu, James R. Marshall, T. C. Hsu and Stimson P. Schantz. Marijuana Use and Increased Risk of Squamous Cell Carcinoma of the Head and Neck. Cancer

Epidemiology, Biomarkers & Prevention, 8(1071), 1999, 1071-8.

17. Tzu-Chin WU, Donald P. Tashkin, Behnam Djahed, Jed E. Rose. Pulmonary hazards of smoking marijuana as compared with tobacco. New England Journal of Medicine, 318(6), 1988, 347-51.

Documents

EFFECTS OF CANNABIS – A REVIEW