Thoughts from the void: Cannabis and Benzodiazepines

Benzodiazepines are widely used in medicine to treat anxiety and insomnia. Although benzodiazepines are much safer in overdose than their predecessors, the barbiturates, they can still cause problems in overdose. Taken alone, they rarely cause severe complications in overdose; statistics in England showed that benzodiazepines were responsible for 3.8% of all deaths by poisoning from a single drug. However, combining these drugs with alcohol, opiates or tricyclic antidepressants markedly raises the toxicity. The elderly are more sensitive to the side effects of benzodiazepines, and poisoning may even occur from their long-term use. The various benzodiazepines differ in their toxicity; temazepam appears most toxic in overdose and when used with other drugs.The symptoms of a benzodiazepine overdose may include; drowsiness, slurred speech, nystagmus, hypotension, ataxia, coma, respiratory depression, and cardiorespiratory arrest.

Although overdose receives less attention as a benzodiazepine-related adverse event, benzodiazepines are the second-most common medication class involved in pharmaceutical overdose deaths, and overdose deaths that involve benzodiazepines increased more than 6-fold from 1996 through 2014. More than 75% of benzodiazepine-related deaths involve opioids, and evidence continues to accumulate that use of benzodiazepines is associated with increased risk of opioid-related overdose and mortality. In the US, Benzodiazepine co-involvement in all OODs increased nonlinearly from 8.7% in 1999 to 21.0% in 2017. Benzodiazepines were present in 33.1% of prescription OODs and 17.1% of synthetic OODs in 2017. State-level rates of binge drinking were significantly correlated with alcohol co-involvement in all OODs (r=0.34; P=.02). State benzodiazepine prescribing rates were significantly correlated with benzodiazepine co-involvement in all OODs (r=0.57; P<.001)

ICU patients frequently receive opioid and benzodiazepine medications to treat the pain, anxiety, and agitation experienced during a critical illness. Trauma ICU (TICU) patients may require high and/or prolonged doses of opioids to manage pain associated with multiple open wounds, fractures, painful procedures, and/or surgery. They may also require benzodiazepines to prevent or manage anxiety and agitation and to facilitate effective mechanical ventilation (MV). Exposure to high or prolonged use of opioids and benzodiazepines may also contribute to both drug tolerance (increased dose of medication is required to maintain the same effect) and drug physical dependence (abrupt or gradual drug withdrawal causes unpleasant physical symptoms). Once drug dependence has developed, patients are then at risk for withdrawal syndrome (WS), a group of serious physical and psychologic symptoms that occur upon the abrupt discontinuation of these medications. The effect of WS on patient recovery and prolonged ICU stay is unclear.

The elderly are at an increased risk of both short- and long-term adverse effects, and as a result, all benzodiazepines are listed in the Beers List of inappropriate medications for older adults.Given that older adults experienced the largest absolute increases in opioid-related mortality between 2001 and 2016 and also experience the highest rates of coprescribing of opioids and benzodiazepines, benzodiazepine prescribing may be associated with increased opioid-related morbidity and mortality among older adults.

Long-term use of BZRAs [Benzodiazepine receptor agonist] (> four weeks) in older adults should be avoided for most indications because of their minimal efficacy and risk of harm. Older adults have increased sensitivity to BZRAs and decreased ability to metabolize some longer-acting agents, such as diazepam. All BZRAs increase the risk of cognitive impairment, delirium, falls, fractures, hospitalizations, and motor vehicle crashes. Alternative management strategies for insomnia, anxiety disorders, and the behavioural and psychological symptoms of dementia (also known as responsive behaviours) are recommended. BRZAs have minimal efficacy for anxiety, insomnia, or responsive behaviours related to dementia. This is coupled with concerns about their associated adverse effects. These drugs commonly appear on lists of medications to avoid in the care of older patients.

The INCB reported that in 2006, total global licit production of benzodiazepines amounted to at least 180 metric tonnes, 56 tonnes of which was diazepam. Italy (32 %), India (19 %), China (11 %) and Germany (10 %) were the leading manufacturers between 1997 and 2006.

Thirty-three benzodiazepines were included in Schedule IV of the 1971 United Nations Convention on Psychotropic Substances in 1984. Midazolam (1990) and brotizolam (1995) were subsequently added to the Schedule. In 1995, flunitrazepam (CAS 1622-62-4) was transferred from Schedule IV to Schedule III because the International Narcotics Control Board (INCB) stated that it was one of the most misused benzodiazepines and because of its frequent diversion into the illicit market.

Phenazepam (fenazepam) (CAS 51753-57-2), which is used in medical practice in some countries outside of the European Union, is not scheduled in the 1971 United Nations Convention on Psychotropic Substances.'

In the United States, benzodiazepines are Schedule IV drugs under the Federal Controlled Substances Act, even when not on the market (for example, nitrazepam and bromazepam).

Alternative management strategies for insomnia, anxiety disorders, and the behavioural and psychological symptoms of dementia (also known as responsive behaviours) are recommended.

Current users and PU [past users] took MC [Medical Cannabis] to address pain (65.30%), spasms (63.30%), sleeplessness (32.70%), and anxiety (24.00%), and 63.30% reported it offered “great relief” from symptoms. Participants reported that MC is more effective and carries fewer side effects than prescription medications.

Cannabis use was consistently two to three times higher among those with high anxiety compared to those with some or no anxiety and was higher in US states with RML [Recreational Marijuana Legalization] compared to MML [Medical Marijuana Legalization] or no MML/RML. Cannabis use has increased over time among those with and without anxiety overall, in MML states, and in states without MML/RML; with a faster increase in cannabis use among those with high anxiety compared to lower anxiety in states with MML.

Unlike widely used anxiolytic and antidepressant drugs such as benzodiazepines and SSRIs, the acute administration of an anxiolytic dose of Cannabidiol (CBD) does not appear to interfere with the sleep cycle of healthy volunteers.

Following are articles related to the above topic. Words in italics are my thoughts at the time of reading the article.

'The major features of cellular organization, including, for instance, mitosis, must be much older than 500 million years old - more nearly 1000 million,' wrote Geroge Gaylord Simpson and his colleagues Pittendrigh and Tiffany in their broadly encompassing book entitled Life. 'In this sense the world of life, which is surely fragile and complex, is incredibly durable through time - more durable than mountains. This durability is wholly dependent on the almost incredible accuracy with which the inherited information is copied from generation to generation.'

But in all the thousand million years envisioned by these authors no threat has struck so directly and so forcefully at that 'incredible accuracy' as the mid-20th century threat of man-made radiation and man-made and man-disseminated chemicals. Sir Macfarlane Burnet, a distinguished Australian physician and a Nobel Prize winner, considers it 'one of the most significant medical features' of our time that, 'as a by-product of more and more powerful therapeutic procedures and the production of chemical substances outside of biological experiences, the normal protective barriers that kept mutagenic agents from the internal organs have been more and more frequently penetrated.' - Silent Spring, Rachel Carson, 1962

'The full scope of the dangerous interaction of chemicals is as yet little known, but disturbing findings now come regularly from scientific laboratories. Among this is the discovery that that the toxicity of an organic phosphate can be increased by a second agent that is not necessarily an insecticide. For example, one of the plasticizing agents may act even more dangerously than another insecticide to make malathion more dangerous. Again, this is because it inhibits the liver enzyme that would normally 'draw the teeth' of the poisonous insecticide.

What of other chemicals in the normal human environment? What, in particular, of drugs? A bare beginning has been made on this subject, but already it is known that some organic phosphates (parathion and malathion) increase the toxicity of some drugs used as muscle relaxants, and that several others (again including malathion) markedly increase the sleeping time of barbiturates.'

- Silent Spring, Rachel Carson, 1962

'The cure at Lexington is not designed to keep the addicts comfortable. It starts at one-quarter of a grain of M[orphine] three times a day and lasts eight days-the preparation now used is a synthetic morphine called dolophine. After eight days, you get a send-off shot and go over in "population." There you receive barbiturates for three nights and that is the end of medication.
For a man with a heavy habit, this is a very rough schedule. I was lucky, in that I came in sick, so the amount given in the cure was sufficient to fix me. The sicker you are and the longer you have been without junk, the smaller the amount necessary to fix you.' - Junky, William S Burroughs, 1977, originally published in 1953

'"Nembies": after the phrase, "to take the edge off," Burroughs first draft glossary continued; "Sometimes injected intravenously. If you miss the vein you will surely get an abcess. Barbiturates are more dangerous than junk because a user of barbiturates - eight or more capsules per day - gets the horrors when he is cut off barbiturates, and he is subject to epileptic fits with frequent head injury from flopping around on concrete floors. He is most likely to find himself cut off in a place where the floors are concrete." - Junky, William S Burroughs, 1977, originally published in 1953

Cannabis meets all these criteria plus it it naturally growing worldwide and has been used for tens of thousands of years...no need for a new drug, we just need to bring it back..reefer madness had clouded even Huxley's mind at the time that this was written...

'What is needed is a new drug which will relieve and console our suffering species without doing more harm in the long run than it does good in the short. Such a drug must be potent in minute doses and synthesizable. If it does not possess these qualities, its production, like that of wine, beer, spirits and tobacco will interfere with the raising of indispensible food and fibres. It must be less toxic than opium or cocaine, less likely to produce undesirable social consequences than alcohol or the barbiturates, less inimical to the heart and lungs than the tars and nicotine of cigarettes. And, on the positive side, it should produce changes in consciousness more interesting, more intrinsically valuable than mere sedation or dreaminess, delusions of impotence or release from inhibition.' - The Doors of Perception, Aldous Huxley, 1954.

Huxley misses a point or two here..no drug will be universally perfect for all. There will always be a minority (better that than a majority) for whom any drug will be incompatible given different mental and physical constitutions. Also his obsession and faith in the Western system of synthesizing something that can be had in measured doses like pills or alcohol is unnecessary for natural intoxicants where margins are much larger and safer..cannabis is the ideal...peyote and psilocybin too, where it is available, but not to the extent of cannabis...nature has done the work already, no need for pharmacologists and neurologists to re-invent the wheel...

'Although obviously superior to cocaine, opium, alcohol and tobacco, mescalin is not yet the ideal drug. Along with the happily transfigured majority of mescalin takers there is a minority that finds in the drug only hell or purgatory. Moreover, for a drug that is to be used, like alcohol, for general consumption, its effects last for an inconveniently long time. But chemistry and physiology are capable nowadays of practically anything. If the psychologists and sociologists will define the ideal, the neurologists and pharmacologists can be relied upon to discover the means whereby that ideal can be realized or at least (for this kind of ideal can never, in the very nature of things, be fully realized) more nearly approached than in the wine-bibbing past, the whisky-drinking, marijuana- smoking and barbiturate-swallowing present.' - The Doors of Perception, Aldous Huxley, 1954.

'The purpose of this Notice is to inform potential applications to the National Institute on Drug Abuse (NIDA) and National Institute on Aging (NIA) of special interest in grant applications to conduct rigorous research on cannabis and potentially addictive, psychoactive prescription drug use (specifically opioids and benzodiazepine) in older adults. This program will focus on two distinct older adult populations (over the age of 50): (1) individuals with earlier use onset of cannabis and the specified drug classes who are now entering older age, or (2) individuals who initiate use of cannabis and the specified drug classes after the age of 50. Insights gained from this initiative have the potential to inform the public and health care systems regarding use of cannabis and prescription opioids and benzodiazepines in older populations.'
https://grants.nih.gov/grants/guide/notice-files/NOT-DA-20-014.html

'Current users and PU [past users] took MC [Medical Cannabis] to address pain (65.30%), spasms (63.30%), sleeplessness (32.70%), and anxiety (24.00%), and 63.30% reported it offered “great relief” from symptoms. Participants reported that MC is more effective and carries fewer side effects than prescription medications.

Conclusions
Medicinal cannabis is an effective and well-tolerated treatment for a number of SCI[Spinal Cord injury]-related symptoms.'
https://www.nature.com/articles/s41394-019-0208-6

'Results
Cannabis use was consistently two to three times higher among those with high anxiety compared to those with some or no anxiety and was higher in states with RML [Recreational Marijuana Legalization] compared to MML [Medical Marijuana Legalization] or no MML/RML. Cannabis use has increased over time among those with and without anxiety overall, in MML states, and in states without MML/RML; with a faster increase in cannabis use among those with high anxiety compared to lower anxiety in states with MML.

Conclusions
Cannabis use is increasing among American adults overall, yet is disproportionately common among Americans with anxiety especially among those residing in states where cannabis has been legalized.'
https://www.sciencedirect.com/science/article/abs/pii/S0376871620303288

'Where data are available, they show a steady decline in the use of NPS in Europe, but such substances have established themselves in some marginalized groups in society, such as the homeless or people in prison, among whom the smoking of synthetic cannabinoids has been identified as a problem. In Europe, the use of NPS in prisons was reported by 22 countries, with synthetic cannabinoids identified as posing the main challenge and health risks (16 countries), whereas the use of synthetic cathinones in prisons was reported by 10 countries, NPS with opioid effects by six, and new benzodiazepines by four countries. In Latvia, the use of synthetic opioids in prisons has also been linked to an increase in overdose cases and in injecting drugs and sharing needles among prisoners who use drugs.' - United Nations Office on Drugs and Crime, World Drug Report 2020, https://wdr.unodc.org/wdr2020/field/WDR20_BOOKLET_4.pdf

'The non-medical use of tramadol among other pharmaceutical drugs is reported by several countries in South Asia: Bhutan, India, Nepal and Sri Lanka. In 2017, 130,316 capsules containing tramadol and marketed under the trade name “Spasmo Proxyvon Plus (‘SP+’)” were seized in Bhutan. In Sri Lanka, about 0.2 per cent of the population aged 14 and older are estimated to have misused pharmaceutical drugs in the past year. Among them, the non-medical use of tramadol is the most common, although misuse of morphine, diazepam, flunitrazepam and pregabalin have also been reported in the country. The misuse of more than one pharmaceutical drug (including tramadol) is also a common pattern among heroin users who may use them to potentiate the effects of heroin or compensate for its low level of availability. Recent seizures of tramadol suggest the existence of a market for the drug: in April and September 2018, 200,000 and 1.5 million tablets of tramadol were respectively seized by customs in Sri Lanka.' - United Nations Office on Drugs and Crime, World Drug Report 2020, https://wdr.unodc.org/wdr2020/field/WDR20_BOOKLET_4.pdf

'In the Sudan, while population-based estimates of the extent of substance use are not available, research suggests that the drug scene has rapidly changed, especially with the increasing non-medical use of pharmaceutical drugs among young people, including tramadol, benzodiazepines, cough syrups and antihistamines, trihexyphenidyl, anticonvulsants and neuropathic pain agents such as pregabalin and gabapentin.' - United Nations Office on Drugs and Crime, World Drug Report 2020, https://wdr.unodc.org/wdr2020/field/WDR20_BOOKLET_4.pdf

'The current crisis of fentanyls appears to be more supply-driven than earlier waves of increases in the use of pharmaceutical opioids or heroin. Fentanyls are being used as an adulterant of heroin, are used to make falsified pharmaceutical opioids, such as falsified oxycodone and hydrocodone – and even falsified benzodiazepines – which are sold to a large and unsuspecting population of users of opioids and other drugs; users are not seeking fentanyl as such.

It seems that some local distributors are not able to distinguish between heroin, fentanyl and fentanyl laced heroin, nor between diverted pharmaceutical opioids and falsified opioids containing fentanyl. A general problem with fentanyls is dosing by nonprofessional “pharmacists”, where small mistakes can lead to lethal results. Furthermore, as the overdose death data suggest, even people using cocaine and psychostimulants, such as methamphetamine, are also exposed – probably unintentionally – to fentanyls or other potent synthetic opioids mixed with those substances' - United Nations Office on Drugs and Crime, World Drug Report 2020, https://wdr.unodc.org/wdr2020/field/WDR20_BOOKLET_4.pdf

Ganja in the Indian sub-continent...

'The urge to transcend self-conscious selfhood is, as I have said, a principal appetite of the soul. When, for whatever reason, men and women fail to transcend themselves by means of worhip, good works and spiritual exercises, they are apt to resort to religion's chemical surrogates - alcohol and 'goof-pills' in the modern West, alcohol and opium in the East, hashish in the Mohameddan world, alcohol and marijuana in Central America, alcohol and coca in the Andes, alcohol and the barbiturates in the more up-to-date regions of South America.' - The Doors of Perception, Aldous Huxley, 1954.

'Limiting access to lethal means is a proven way to prevent suicides. Smaller pack size and blister packaging proved protective against suicide by paracetamol. To reduce suicide risk, we recommend blister packing all opioids and other potentially lethal drugs. Suicidal acts often are impulsive, and once underway, the individual is impatient. Youths, in particular, are likely to simply choose a different bottle rather than patiently empty blister packs.

Adults used more considered drug mixes than youths. Their mixes increased lethality. It is unclear why adults had higher mortality rates than youths when they included alcohol in their mix. Possibly they took more drugs that interacted adversely with alcohol. Conversely, alcohol use disorder is a known risk factor for suicide. Therefore, alcohol involvement among adults might serve as a marker for alcohol use disorders that focused attempters on more lethal drug mixes. Antidepressant involvement might provide a similar signal.'
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7090840/

'Although evidence suggests that loneliness may increase risk for health problems, the mechanisms responsible are not well understood. Immune dysregulation is one potential pathway: Elevated proinflammatory cytokines such as interleukin-6 (IL-6) increase risk for health problems. In our first study (N = 134), lonelier healthy adults exposed to acute stress exhibited greater synthesis of tumor necrosis factor-alpha (TNF-a) and IL-6 by peripheral blood mononuclear cells (PBMCs) stimulated with lipopolysaccharide (LPS) than their less lonely counterparts. Similarly, in the second study (N = 144), lonelier posttreatment breast-cancer survivors exposed to acute stress exhibited greater synthesis of IL-6 and interleukin-1 beta (IL-1ß) by LPS-stimulated PBMCs than their counterparts who felt more socially connected. However, loneliness was unrelated to TNF-a in Study 2, although the result was in the expected direction. Thus, two different populations demonstrated that lonelier participants had more stimulated cytokine production in response to stress than less lonely participants, which reflects a proinflammatory phenotype. These data provide a glimpse into the pathways through which loneliness may affect health'
https://www.ncbi.nlm.nih.gov/pubmed/23630220/

'Long-term use of BZRAs [Benzodiazepine receptor agonist] (> four weeks) in older adults should be avoided for most indications because of their minimal efficacy and risk of harm. Older adults have increased sensitivity to BZRAs and decreased ability to metabolize some longer-acting agents, such as diazepam. All BZRAs increase the risk of cognitive impairment, delirium, falls, fractures, hospitalizations, and motor vehicle crashes. Alternative management strategies for insomnia, anxiety disorders, and the behavioural and psychological symptoms of dementia (also known as responsive behaviours) are recommended. BRZAs have minimal efficacy for anxiety, insomnia, or responsive behaviours related to dementia. This is coupled with concerns about their associated adverse effects. These drugs commonly appear on lists of medications to avoid in the care of older patients'
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7067147/

'The INCB reported that in 2006, total global licit production of benzodiazepines amounted to at least 180 metric tonnes, 56 tonnes of which was diazepam. Italy (32 %), India (19 %), China (11 %) and Germany (10 %) were the leading manufacturers between 1997 and 2006.'
http://www.emcdda.europa.eu/publications/drug-profiles/benzodiazepines_en

This also implies reduced use of opioids, benzodiazepines and analgesics...key factors in increased fatalities among men in recent years in the US..

'Among those who acknowledged using cannabis for medical purposes, 49 percent reported doing so to treat anxiety. Forty-seven percent of respondents said that they used cannabis for insomnia, 42 percent said that they did so to treat chronic pain, and 39 percent said that cannabis eased their depression.

Respondents most preferred method of cannabis ingestion was inhalation.

Women, more frequently than men, reported using cannabis to address symptoms of post-traumatic stress, insomnia, anxiety, and migraines. Men were more likely to report using cannabis as a mood stabilizer.'
https://norml.org/news/2020/04/30/survey-cannabis-often-used-to-mitigate-symptoms-of-anxiety-insomnia-and-chronic-pain

'From 1999 to 2017, 399 230 poisoning deaths involved opioids, of which 263 601 (66.0%) were male, and 204 560 (51.2%) were aged 35 to 54 years. Alcohol co-involvement for all opioid overdose deaths increased nonlinearly from 12.4% in 1999 to 14.7% in 2017. By opioid subtype, deaths involving heroin and synthetic opioids (eg, fentanyl; excluding methadone) had the highest alcohol co-involvement at 15.5% and 14.9%, respectively, in 2017. Benzodiazepine co-involvement in all OODs increased nonlinearly from 8.7% in 1999 to 21.0% in 2017. Benzodiazepines were present in 33.1% of prescription OODs and 17.1% of synthetic OODs in 2017. State-level rates of binge drinking were significantly correlated with alcohol co-involvement in all OODs (r=0.34; P=.02). State benzodiazepine prescribing rates were significantly correlated with benzodiazepine co-involvement in all OODs (r=0.57; P<.001)'
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7146101/

'These findings represent part of a wider pattern of increasingly widespread adult use of prescribed medicines that are associated with problems of dependence and withdrawal. In 2019, Public Health England published a review of prescription drug dependence. As well as opioids for chronic pain, the review studied patterns of use of benzodiazepines, Z-drugs (non-benzodiazepine hypnotics), gabapentinoids and antidepressants. The review found that in 2017–18, 26% of the adult population had some exposure to these medicines including antidepressants (17% of the adult population), opioids (13%), gabapentinoids (3%), benzodiazepines (3%) and Z-drugs (2%). Long-term prescribing of these medicines was found to be widespread, with evidence of dependence and difficulties of withdrawal.'
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7167503/

'ICU patients frequently receive opioid and benzodiazepine medications to treat the pain, anxiety, and agitation experienced during a critical illness. Trauma ICU (TICU) patients may require high and/or prolonged doses of opioids to manage pain associated with multiple open wounds, fractures, painful procedures, and/or surgery. They may also require benzodiazepines to prevent or manage anxiety and agitation and to facilitate effective mechanical ventilation (MV).

Although the effect of different pain and sedative medication regimens on TICU patients is unclear, prior evidence suggests that administration of opioid and benzodiazepine medications in the ICU setting is associated with the development of many complications including delirium and poor patient outcomes (e.g. longer days spent on MV and longer ICU and hospital stays). Exposure to high or prolonged use of opioids and benzodiazepines may also contribute to both drug tolerance (increased dose of medication is required to maintain the same effect) and drug physical dependence (abrupt or gradual drug withdrawal causes unpleasant physical symptoms). Once drug dependence has developed, patients are then at risk for withdrawal syndrome (WS), a group of serious physical and psychologic symptoms that occur upon the abrupt discontinuation of these medications. The effect of WS on patient recovery and prolonged ICU stay is unclear.'
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7188437/

Flunitrazepam (Rohypnol®) is the benzodiazepine most commonly linked by media reports to drug-facilitated sexual assaults, more commonly referred to as ‘date rape’. However, forensic toxicology shows that only a very small number of such assaults actually involve the use of flunitrazepam. A number of studies, cited in the EMCDDA Technical data sheet on Sexual assaults facilitated by drugs or alcohol (EMCDDA 2008), suggest that alcohol and other benzodiazepines are an underestimated problem in such cases.'
http://www.emcdda.europa.eu/publications/drug-profiles/benzodiazepines_en

'Thirty-three benzodiazepines were included in Schedule IV of the 1971 United Nations Convention on Psychotropic Substances in 1984 (Table 1). Midazolam (1990) and brotizolam (1995) were subsequently added to the Schedule. In 1995, flunitrazepam (CAS 1622-62-4) was transferred from Schedule IV to Schedule III because the International Narcotics Control Board (INCB) stated that it was one of the most misused benzodiazepines and because of its frequent diversion into the illicit market.

Phenazepam (fenazepam) (CAS 51753-57-2), which is used in medical practice in some countries outside of the European Union, is not scheduled in the 1971 United Nations Convention on Psychotropic Substances.'
http://www.emcdda.europa.eu/publications/drug-profiles/benzodiazepines_en

'https://en.wikipedia.org/wiki/Benzodiazepine

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7125434/

'Unlike widely used anxiolytic and antidepressant drugs such as benzodiazepines and SSRIs, the acute administration of an anxiolytic dose of CBD does not appear to interfere with the sleep cycle of healthy volunteers. Future studies should address the effects of CBD on the sleep-wake cycle of patient populations as well as evaluate the chronic effects of CBD in larger samples of patients with sleep and neuropsychiatric disorders.'
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5895650/

'Although overdose receives less attention as a benzodiazepine-related adverse event, benzodiazepines are the second-most common medication class involved in pharmaceutical overdose deaths, and overdose deaths that involve benzodiazepines increased more than 6-fold from 1996 through 2014. More than 75% of benzodiazepine-related deaths involve opioids, and evidence continues to accumulate that use of benzodiazepines is associated with increased risk of opioid-related overdose and mortality. Given that older adults experienced the largest absolute increases in opioid-related mortality between 2001 and 20169 and also experience the highest rates of coprescribing of opioids and benzodiazepines, benzodiazepine prescribing may be associated with increased opioid-related morbidity and mortality among older adults.'
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7125434/

Can the benzodiazipines please be substituted with cannabis and natural cannabis be legalized for people to access world wide?

'With regard to CBD's safety, they concluded: "[M]ost studies reported no adverse events with acute administration and mild to moderate adverse effects with chronic administration. In comparison to other drugs, a better side effect profile was presented.'
https://norml.org/news/2020/04/16/review-oral-use-of-cbd-reports-anxiolytic-and-anti-psychotic-activity-few-adverse-effects

'Top Trump administration officials say drug overdose deaths are surging amid the coronavirus pandemic, driven by increased substance use due to anxiety, social isolation and depression.

A White House drug policy office analysis shows an 11.4 percent year-over-year increase in fatalities for the first four months of 2020, confirming experts’ early fears that precautions like quarantines and lockdowns combined with economic uncertainty would exacerbate the addiction crisis'
https://www.politico.com/news/2020/06/29/pandemic-unleashes-a-spike-in-overdose-deaths-345183

'Pennsylvanians suffering from anxiety may soon be able to treat the disorder with medical marijuana.

The state Medical Marijuana Advisory Board on Friday voted to add anxiety and Tourette syndrome as conditions qualifying patients to buy medicinal cannabis at dispensaries across the state.'
https://www.mcall.com/business/healthcare/mc-biz-medical-marijuana-news-anxiety-tourettes-edibles-20190201-story.html

'Main Outcome Measures: Sleep and anxiety scores, using validated instruments, at baseline and after CBD treatment.

Results: The final sample consisted of 72 adults presenting with primary concerns of anxiety (n = 47) or poor sleep (n = 25). Anxiety scores decreased within the first month in 57 patients (79.2%) and remained decreased during the study duration. Sleep scores improved within the first month in 48 patients (66.7%) but fluctuated over time. In this chart review, CBD was well tolerated in all but 3 patients.

Conclusion: Cannabidiol may hold benefit for anxiety-related disorders. Controlled clinical studies are needed.'
http://www.thepermanentejournal.org/issues/2019/winter/6960-cannabis.html

'More importantly, the results get us closer to understanding how CBD interacts with neurons in entirely different ways than its well-known partner compound, THC – sidestepping drawbacks of affecting the endocannabinoid system in the process. And if these findings replicate in humans, we’re also closer to harnessing CBD’s potential to deliver non-addictive pain and anxiety relief, offering patients on highly addictive opioids and benzodiazepine anti-anxiety meds another way to go.'
https://www.forbes.com/sites/daviddisalvo/2018/10/29/study-cbd-may-provide-pain-and-anxiety-relief-in-different-ways-than-previously-thought/

'The study, published in the Brazilian Journal of Psychiatry, tested how CBD influences anxiety in a simulated public speaking setting, “a well-tested anxiety-inducing method.”'
https://www.marijuanamoment.net/marijuana-ingredient-reduces-anxiety-during-public-speaking-study-shows/

'The most common conditions for which CBD was either discussed or recommended were pain management, anxiety, seizures and storm or fireworks phobias, according to the survey.'
https://www.marijuanamoment.net/veterinarians-want-marijuana-laws-loosened-for-pets-and-humans-survey-finds/

“I believe that advanced dementia patients with tremendous anxiety, restlessness, and pain will benefit,” he wrote. “Such patients are episodically distraught and become quickly angered and paranoid of staff trying to help them due to their confusion and inability to understand their circumstances.”'
http://www.startribune.com/alzheimer-s-added-to-minnesota-s-medical-marijuana-list/501803661/

'Opioid addiction, autism, general anxiety, chronic anxiety, depression and insomnia were selected Wednesday for more study as qualifying conditions for medical marijuana in Ohio.

A committee of the Ohio State Medical Board met in Columbus to select those conditions as Ohio prepares for the first sales of medical marijuana, perhaps as early as next week.'
https://www.cincinnati.com/story/news/2019/01/09/ohio-study-more-ailments-medical-marijuana/2529672002/

'The top three reasons why consumers use cannabis are for relaxation (66%), stress relief (59%) and to reduce anxiety (53%). Nevertheless, small percentages use cannabis for a long list of reasons. including to improve their sleep, treat medical conditions, enjoy social experiences, and stimulate creativity.'
https://newfrontierdata.com/marijuana-insights/with-archetypes-cannabis-industry-meets-customers-in-the-open-market/

Conclusions: Anxiety was a common reason for using cannabis among older adults. Overall, use of cannabis for anxiety is perceived to be helpful in alleviating symptoms. More research on cannabis in older adults is warranted including prevalence of use, efficacy in treating anxiety, and potential changes in concurrently prescribed anxiolytic medications as a result of cannabis use.'
https://www.sciencedirect.com/science/article/abs/pii/S1064748120301238

'Authors further reported that cannabis therapy was associated with a reduction in subjects' use of prescription medications – a finding that is consistent with prior studies. Overall, participants discontinued taking a total of 39 prescription medicines during the study period. Patients were most likely to eliminate their use of opioids, anxiolytics, and anti-depressants after initiating cannabis therapy.

They concluded, "We found an overall improvement in the patients, including of their symptoms and medical conditions, cessation or reduction of traditional drug usage, and a general improvement in life quality. ... Overall, 39 dosages of prescription drugs were cancelled for the 19 elderly individuals included in this research, indicating that medical cannabis can be an effective treatment that also reduces environmental drug load."'
https://norml.org/news/2020/06/11/study-medical-cannabis-therapy-reduces-prescription-drug-use-among-nursing-home-patients

'In addition to alcohol, some older adults have also been found to be drug abusers (Li and Jackson, 2016). These drugs include prescription drugs and illicit drugs. Older people are reported to have the highest prescription-drug abuse rate of any other age group (Briggs et al., 2011). Among the prescription drugs, benzodiazepines and opioid analgesics are frequently prescribed to individuals aged 65 years and older. In Australia’s aged care services, around 4.4 percent of residents report misusing opioids or benzodiazepines (Li and Jackson, 2016).'
http://journals.sagepub.com/doi/full/10.1177/2055102917708136