Research

Abstract Cannabis is the most commonly abused drug in the world. In Egypt, the Anti Narcotic General Administration showed that the narcotics problem costs the Egyptian economy approximately 800 million dollars annually. LD50, lethal dose that kills 50% of the treated animals, of the bango was determined and then selected groups of rats were given tenth of LD50 for 90 days.
All over the world, there is growing interest in the part played by drugs in traffic accidents, and how to investigate adequate measures to reduce their incidence.2 Africa is the second largest producer of herbal cannabis in the world.3 In Egypt, drug addiction is considered one of the serious problems that worry both people and government. It affects young people within their productive years. It may lead to many problems such as social maladaptation, decreased works productivity and job loss.4 ‘Bango’ is the name of cannabis leaves used in Egypt and North Africa.5
Conclusion In conclusion, the present study revealed the bad effects of the bango plant on different organs in animals. Bango abuse leads to severe effects on different organs and this may subsequently lead to apoptosis and fibrosis of the organs, and this depends mainly on the dose and duration of administration.

The evidence presented in this review allows us to conclude that Δ9-THC and CBD produce biphasic, dose-dependent effects on several physiological responses. The biphasic nature of cannabinoid effects highlights the need for a careful analysis of the dose ranges separating therapeutic from unwanted effects. Besides, Δ9-THC produces dependence and harmful effects, while CBD does not.
The available pharmaceutical formulations of these phytocannabinoids and related molecules have clear therapeutic effects; however, more research is needed to assure their efficacy and safety since their effects are complex. Several additional potential therapeutic applications, mainly for CBD, are being proposed which, however, still lack sufficient clinical and preclinical support. For this reason, caution is advised when using or prescribing cannabinoids.
Additional consideration deserves the fact that the ECS participates in the development of the central nervous system98. Therefore, the use of cannabinoid-based formulations for the medical treatment of children and adolescents experiencing brain developmental changes must be carefully examined, balancing the pros and cons of prescribing cannabinoid-based medications in every single case. Cannabis research field is expanding with the identification of new molecular targets, the characterization of undescribed phytocannabinoids, and novel findings related to the ECS99. In addition, consumption of synthetic cannabinoids as drugs of abuse represents a new challenge in addiction research100.

Conclusions: This is the first characterization of the effect of cannabis exposure on the entirety of the rat sperm methylome. We identified CE-associated methylation changes across the sperm methylome, some of which persisted despite a "washout" period. Select methylation changes validated via bisulfite pyrosequencing, and genes associated with methylation changes were involved in early developmental processes. Preconception CE exposure is associated with detectable changes in offspring DNA methylation that are functionally related to changes in gene expression and cardiomegaly. These results support that paternal preconception exposure to cannabis can influence offspring outcomes.     

Research has found that prenatal cannabis use may adversely affect fetal growth and neurodevelopment, be associated with future learning and behavioral problems in children, and increase risk of neonatal morbidity. (Cornelius et al., 2002; Day et al., 1994; El Marroun et al., 2011; Fried and Smith, 2001; Fried et al., 1999; Fried et al., 2003; Fried et al., 1997; Goldschmidt et al., 2000; Goldschmidt et al., 2008; Goldschmidt et al., 2012; Metz et al., 2017; Noland et al., 2005; Willford et al., 2010; Ryan et al., 2018; El Marroun et al., 2018) Several US organizations, including the American College of Obstetricians and Gynecologists and the American Academy of Pediatrics, recommend abstinence from cannabis use during pregnancy. (Ryan et al., 2018; Gynecologists, T.A.C.O.O.A, 2020) Despite these recommendations, there are concerns that the trend of cannabis use during pregnancy will continue to increase as more states and countries legalize cannabis and allow for commercial sales through dispensaries. (Mark and Terplan, 2017)

An analysis of survey data from more than 280,000 young adults ages 18-35 showed that cannabis (marijuana) use was associated with increased risks of thoughts of suicide (suicidal ideation), suicide plan, and suicide attempt. These associations remained regardless of whether someone was also experiencing depression, and the risks were greater for women than for men.
“Suicide is a leading cause of death among young adults in the United States, and the findings of this study offer important information that may help us reduce this risk,”

To look for longer-term effects of cannabis, the experimenters called the subjects back a week later and tested them again on the word lists, this time with a few different dummy words thrown in. They also re-interviewed the subjects about the VR scenarios using a combination of old and new questions. As before, they found lower memory accuracy in the word-association test in those who had been intoxicated compared with sober participants. There were no statistically significant differences between the groups for the virtual reality scenarios, a result that Kloft says may indicate memory decay over time in all participants.

In conclusion, our findings confirm previous evidence of the harmful effect on mental health of daily use of cannabis, especially of high-potency types. Importantly, they indicate for the first time how cannabis use affects the incidence of psychotic disorder. Therefore, it is of public health importance to acknowledge alongside the potential medicinal properties of some cannabis constituents the potential adverse effects that are associated with daily cannabis use, especially of high-potency varieties.

Conclusions: Our findings disconfirm the hypothesis that a population-level negative correlation between medical marijuana use and prescription drug harms occurs because medical marijuana users are less likely to use prescription drugs, either medically or nonmedically. Medical marijuana users should be a target population in efforts to combat nonmedical prescription drug use.

1. Legalizing cannabis has been shown to increase the rates of motor vehicle accidents.
2. Cannabis use is a risk factor for mental illness.
3. Inhaled Cannabis use is a risk factor for respiratory infections.
4. Cannabis use increases the rate of vascular disease. Cannabis is the third most often identified drug of abuse
5. Cannabis use during pregnancy has been associated with increased risk of adverse birth outcomes
6. Legalization of cannabis has been shown to increase cannabis exposure in the pediatric population.
7. Heavy cannabis use is associated with diminished lifetime achievements.
Doctors must educate the public about the potential harm cannabis causes with heavy, and possibly moderate, widespread use just as they do about the dangers of tobacco use. Tobacco use has declined in the United States in large part because of the knowledge the public now holds about its adverse effects, as opposed to legislative action.

Similarly, it can be anticipated that if introduced, the indications for the  use of medical cannabinoids would expand well outside of the initial indications. Hence, the medical profession cannot justify the use of medical cannabinoids that would be associated with an iatrogenic risk of serious adverse psychological events.  The use of medical cannabinoids for any purpose, including research under closely observed conditions, is incompatible with mental health promotion.

The existence of hallucinations, delusions, and organic brain dysfunction in heavy cannabis users seems to be associated with cannabinoid levels in hair. The continuation of persistent symptoms 3 months after the discontinuation of cannabis abuse, was a remarkable finding. SCIENTIFIC SIGNIFICANCE: We provide evidence that chronic and heavy cannabis abuse results in long-lasting brain dysfunction in all users and in long-lasting schizophrenia-like psychotic symptoms in more than half of all users. These findings suggest a reevaluation of the current classification of cannabis as a "soft narcotic" which erroneously, therefore, is typically considered harmless. (Am J Addict 2017;XX:1-8).

According to research studies, marijuana use causes aggressive behavior, causes or exacerbates psychosis and produce paranoias. These effects have been illustrated through case studies of highly publicized incidents and heightened political profiles.

Marijuana is currently a growing risk to the public in the United States. Following expanding public opinion that marijuana provides little risk to health, state and federal legislatures have begun changing laws that will significantly increase accessibility of marijuana. Greater marijuana accessibility, resulting in more use, will lead to increased health risks in all demographic categories across the country. Violence is a well-publicized, prominent risk from the more potent, current marijuana available.

A common theme among every article in this issue is the overlap be- tween NMUPD, excessive drinking, and marijuana and other forms of substance use. In every investigation, nonmedical users were observed to have a history of using alcohol, marijuana, tobacco, and other psycho- active substances. Kalyanam, Katsuki, Lanckriet, and Mackey (2017)
Kalyanam, J., Katsuki, T., Lanckriet, G., & Mackey, T. K. (2017). Exploring trends of non- medical use of prescription drugs and polydrug abuse in the Twittersphere using un- supervised machine learning. Addictive Behaviors, 65, 289–295. http://dx.doi.org/10. 1016/j.addbeh.2016.08.019.

In summary, marijuana use is harmful to children and adolescents.  For this reason, the American College of Pediatricians opposes its legalization for recreational use and urges extreme caution in legalizing it for medicinal use.  Likewise, the American Academy of Child and Adolescent Psychiatry (AACAP) recently offered their own policy statement opposing efforts to legalize marijuana. They similarly pointed out that “marijuana’s deleterious effects on adolescent brain development, cognition, and social functioning may have immediate and long-term implications, including increased risk of motor vehicle accidents, sexual victimization, academic failure, lasting decline in intelligence measures, psychopathology, addiction, and psychosocial and occupational impairment.” Thus the AACAP (a) opposes efforts to legalize marijuana, (b) supports initiatives to increase awareness of marijuana’s harmful effects on adolescents, (c) supports improved access to evidence-based treatment, rather than emphasis on criminal charges, for adolescents with cannabis use disorder, and (d) supports careful monitoring of the effects of marijuana-related policy changes on child and adolescent mental health.⁴⁹ The College agrees with this position on marijuana.

Although studies are beginning to show that some ingredients in marijuana are likely to be helpful for people with certain conditions, the findings have yet to nail down the specifics about the dose, the frequency, the best form to take (such as getting the active compounds from edible products or smoking it), the risks from frequent use, and whether marijuana works as well as or better than other available treatments, Budney said.
Usage Doubles & Addiction Doubles:  Over this 12-year period, the estimated number of U.S. adults who had used marijuana in the previous 12 months grew from 4.1 percent in 2001 to 9.5 percent in 2013. Marijuana-use disorders, which include problems with drug addiction and dependence, also rose, increasing from 1.5 percent of the adult population in 2001 to 2.9 percent in 2013, the study showed.
 
 College students smoke more pot than cigarettes: The survey found that 5.9 percent of college students said they had smoked pot 20 or more times in the past month. For comparison, 5.2 percent of students reported they had smoked cigarettes 20 or more times in the past month, according to the study. 
Inaccurate Labeling Edibles: Only 13 of the 75 tested pot food products — such as baked goods, beverages and candy — bought from dispensaries in California and Washington state had labels that accurately listed the amount of tetrahydrocannabinol, or THC, 
Teen Brain:  The researchers found that teens who had smoked marijuana — even once — had smaller brain volume in the amygdala compared with teens who never tried pot.
 

The American Medical Association (AMA) has opposed legalizing marijuana for medical use for many years due to the lack of evidence to support such action. In addition to AMA, the following medical associations also oppose legalizing marijuana or any of its components for medical use before FDA-quality evidence is available.

Given these statistics.... is legalization worth the consequences....
Cannabis has been found to be the most frequently used drug in the U.S. after alcohol, tobacco and caffeine. 
The risk of developing addiction associated with cannabis use has been reported to increase to about 17% among those who start using marijuana in adolescence, and to 25-50% among those who smoke marijuana daily.
The long-term effects of marijuana use include altered brain development and cognitive impairment, including impaired neural connectivity in specific brain regions, decreased activity in prefrontal regions, and reduced volumes in the hippocampus.
Cannabis is most commonly consumed through smoking, a route of drug delivery that predictably has a variety of negative effects on pulmonary function. Smoke from marijuana combustion has been shown to contain a number of carcinogens and cocarcinogens, as well as many of the toxins, irritants, and carcinogens as tobacco smoke.  Additionally, marijuana smokers tend to inhale more deeply and hold their breath longer than cigarette smokers, which leads to a greater exposure per breath to “tar” (the carcinogenic solids in smoke). Regular smoking of marijuana, in the absence of tobacco, produces visible and microscopic injury to the large airways
http://www.asam.org/docs/default-source/publicy-policy-statements/mariju...

Brain abnormalities and memory problems were observed in these individuals in their early twenties, two years after they had stopped using marijuana. The cannabis users were noted to have striatal, globus pallidus, and thalamus changes showing these brain regions appearing to shrink and collapse inward. These individuals also had poorer working memory. The earlier the age of cannabis use, the more dramatic the brain changes and memory deficits were noted to be.
Not only does it appear that cannabis use itself is a potential precursor to future drug use, but the age of first use of cannabis and the frequency of cannabis use seem to also be predictors of future substance abuse issues. Studies have shown that over two-thirds of those under the age of 18 who have been admitted to a drug treatment program identify cannabis as their substance of choice.
” One important characteristic that defines a substance use disorder is “an underlying change in brain circuits that may persist beyond detoxification, particularly in individuals with severe disorder"

The principal psychoactive constituent of cannabis is Δ9-tetrahydrocannabinol (THC). THC administered intravenously is characterized by the appearance of psychopharmocological effects within 5 minutes, which continue for at least 90 minutes, providing an excellent experimental window.[12] In within-subjects tests with nonclinical volunteers, D'Souza, in particular, has shown that intravenous administration of THC causes schizophrenia-like symptoms, perceptual disturbances, anxiety, and impaired working memory (eg, Morrison et al[13] and D'Souza et al[14,15]). Similar but more pronounced results were found in patients with schizophrenia.[15]

Studies show that children exposed to marijuana in utero have lower scores on tests of visual problem-solving, visual and motor coordination, and visual analysis, compared with children not exposed to the drug, the report states. Prenatal marijuana exposure also has been associated with decreased attention span and behavioral problems. The nervous system of a human fetus can respond to the chemicals in marijuana within 14 weeks of gestation, and studies have shown that 14-year-olds are more likely to be marijuana users if their mothers used the drug during pregnancy.

Marijuana use for medical conditions is an issue of growing concern. Some Veterans use marijuana to relieve symptoms of PTSD and several states specifically approve the use of medical marijuana for PTSD. However, controlled studies have not been conducted to evaluate the safety or effectiveness of medical marijuana for PTSD. Thus, there is no evidence at this time that marijuana is an effective treatment for PTSD. In fact, research suggests that marijuana can be harmful to individuals with PTSD.

Experts agree, however, that the combination of cannabis and alcohol raises the chance of crashing more than either substance by itself. In a study of 1,882 motor vehicle deaths, the U.S. Department of Transportation found an increased accident risk of 0.7 for cannabis use, 7.4 for alcohol use, and 8.4 for cannabis and alcohol use combined.

Participants in a study who had used the drug daily for around three years in their teens had an abnormally shaped hippocampus by the time they were in their early 20s.
They also performed around 18 per cent worse in long-term memory tests than individuals who had never touched the drug.

·        These consequences include impaired short-term memory and decreased concentration, attention span, and problem solving, which clearly interfere with learning. Alterations in motor control, coordination, judgment, reaction time, and tracking ability have also been documented; these may contribute to unintentional deaths and injuries among adolescents (especially those associated with motor vehicles if adolescents drive while intoxicated by marijuana).
·        Negative health effects on lung function associated with smoking marijuana have also been documented, and studies linking marijuana use with higher rates of psychosis in patients with a predisposition to schizophrenia have recently been published, raising concerns about longer-term psychiatric effects. New research has also demonstrated that the adolescent brain, particularly the prefrontal cortex areas controlling judgment and decision-making, is not fully developed until the mid-20s, raising questions about how any substance use may affect the developing brain. Research has shown that the younger an adolescent begins using drugs, including marijuana, the more likely it is that drug dependence or addiction will develop in adulthood.
·         A recent analysis of 4 large epidemiologic trials found that marijuana use during adolescence is associated with reductions in the odds of high school completion and degree attainment and increases in the use of other illicit drugs and suicide attempts in a dose-dependent fashion that suggests that marijuana use is causative.

States that legalized medical marijuana had higher rates of marijuana use. Future research needs to examine whether the association is causal, or is due to an underlying common cause, such as community norms supportive of the legalization of medical marijuana and of marijuana use.

The authors review literature showing that marijuana impairs driving, increasing the risk of being involved in a car accident and that these risks are further enhanced when combining marijuana with alcohol.

A new study suggests people with mental illness are more than seven times as likely to use marijuana weekly than people without a mental illness.

In total, 4.4 percent of individuals with a mental illness in the past 12 months reported using cannabis weekly, compared to 0.6 percent among individuals without any mental illness.

Cannabis use disorders occurred among 4 percent of those with mental illness versus 0.4 per cent among those without.

Researchers also noted that, although cannabis use is generally higher among younger people, the association between mental illness and cannabis use was pervasive across most age groups.

Conclusions/Significance: Sustained cannabis abstinence moderately improved critical tracking and divided attention performance in chronic, daily cannabis smokers, but impairment was still observable compared to controls after 3 weeks of 

abstinence. Between group differences, however, need to be interpreted with caution as chronic smokers and controls were not matched for education, social economic status, life style and race.