Cannabis research through the ages | 药用大麻研究史

Since the first scientific reports on medical cannabis in the mid-19th-century, research of medicinal cannabis has exponentially expanded. Over 35,000 cannabis studies or research pieces have been published under Pubmed, with more than 19,000 in the past 10 years.

The history of medical cannabis has been entwined with human evolution for at least ten thousand years. Translating its historical use into modern scientific paradigms is an ever-evolving challenge for researchers.

Being a botanical-based medicine with extensive and variable medicinal constituents can make it difficult to study under the controlled conditions by which most medicines are evaluated. Prohibition and stigmatisation in modern history have further stymied progress in research.

However, as we come to understand more about specific cannabinoids’ actions, and as the cloak of stigma and illegality is finally being lifted around the world, well-designed clinical research initiatives, like those at Entoura, have the power to evaluate the benefits of medical cannabis with increasing confidence.

Ancient uses for medical cannabis

The first recorded use of cannabis as a medicine stems from ancient Chinese medicine. Chinese medical texts record cannabis being used in cases of gout, digestive complaints and rheumatism.

Vedic texts derived from India note its benefits in cases of sleep disturbances, anxiety, epilepsy and fevers. Ancient Egyptians recorded using medicinal cannabis preparations for gastrointestinal symptoms, tumours and a range of pain presentations – which in modern-day context may be interpreted as glaucoma, menstrual pain and earaches.

Many of these conditions where cannabis has been applied for hundreds if not thousands of years are now being investigated and validated by modern research.

Cannabis through the ages

Greeks and Romans used cannabis preparations for inflammatory conditions and pain, and in the Americas cannabis was used as pain relief in numerous circumstances, for convulsive disorders and opiate addiction, amongst other things.

In Britain, the famous 17th-century English herbalist Nicholas Culpepper recorded using medical cannabis for joint pain, inflammatory presentations, appetite, menstrual and digestive concerns.

The beginnings of scientific medical cannabis research

The first record of medical cannabis from a scientific lens came in the mid-1800s. Irish physician Dr William O’Shaughnessy is credited with some of the first scientific research conducted on cannabis.

His research encompassed animal and human observations, in the areas of epilepsy, rheumatic joint pain, palliative care and in the alleviation of vomiting from cholera.

Other research followed on from O’Shaughnessy highlighting the use of medicinal cannabis as a sedative, for pain relief, sleep disturbances and found it to be useful in certain psychological presentations.

Medical cannabis research meets a roadblock

Far from facilitating a leap into scientific enlightenment on the therapeutic potential of medicinal cannabis, the 20th-century resulted in a downturn of research in this space in view of international drug conventions and a racially fuelled political maelstrom surrounding the plant, largely stemming from the USA.

And yet, there were some notable breakthroughs. Although the cannabinoid CBD was identified in 1940, the discovery of THC, by Israeli researchers Raphael Mechoulam and YeheilGaoni in 1964 proved to be a launching pad for modern medical cannabis research.

The now famous ‘grandfather of cannabis’ Prof. Mechoulam, spearheaded research into the Endocannabinoid System – our bodies’ innate cannabinoid system that has influence over the immune system, hormonal and sleep patterns, appetite, mood and more.

This discovery has advanced our understanding of this previously unknown regulatory system’s diverse actions within the body, as well as how medical cannabis exerts its therapeutic actions.

However, these initial advancements were very much stifled by the prohibition era, starting as early as 1906 when many US states labelled cannabis as a poison. During the time of cannabis prohibition in the 20th-century, the foundations for modern clinical research, including randomised controlled trials and other scientific methodologies evaluating safety and efficacy, were established. But medical cannabis was left by the wayside, inhibited by local and international regulations from entering the modern medical research structure during such a crucial time of scientific progress.

Over the last 25 years or so, landmark discoveries in the field of cannabinoids and a slow unravelling of prohibition-era restrictions around the world has led to medical cannabis research has become progressively more specific. From trials involving cannabis preparations with little knowledge of the cannabinoid or phytochemical content, to nowadays where clinical trials are conducted for specific conditions with assayed cannabis medicines.

The 1990s and early 2000s bred extensive studies into how medical cannabis might be of use in palliative care, multiple sclerosis, epilepsy and chemotherapy-induced nausea and vomiting.

Research in animal models, human cell lines and clinical trials continue to uncover how cannabinoids may have applications in areas such as tumours, anxiety, PTSD, skin conditions, chemotherapy-induced cachexia/anorexia and a range of autoimmune disorders.

IP challenges in medical cannabis research

One challenge faced in medical cannabis research and product development that can’t be overlooked is that of intellectual property. Being a plant with a long history of use in relatively simple dosage forms (tincture or dried flower), for the majority of current final formulations of medicinal cannabis, it is difficult to generate IP. This has interrupted the traditional pathways for researching products whereby IP leads to research opportunities and funding which progresses a medicine through clinical trials towards products on the shelves.

While it is difficult to generate the IP, nonetheless in Australia, cannabis plants and products are eligible for some IP protections such as patents and plant breeder’s rights when certain criteria are met. And no doubt, as more cannabis licenses are granted and cultivation research expands we are likely to see a further increase in clinical research utilising the plant IP.

Australian medical cannabis research

Entoura is committed to the growth of medical cannabis research and expansion of accessibility for patients. To accomplish this, we engage in collaborations with other eminent medical cannabis companies and instigate our own clinical trials to grow the global understanding of this medicine.

Entoura research into medicinal cannabis and sleep

Sleep can be a dream for some, and a nightmare for others. Medical cannabis preparations have been shown to have therapeutic effects for some people suffering insomnia. Our sleep study aimed to evaluate the safety and effectiveness of medical cannabis on those who have difficulty getting to sleep or staying asleep.

Results demonstrated that Entoura EMC 10:15 medicinal cannabis oil was generally well tolerated, and was found to be effective in improving sleep, melatonin levels, and quality of life.

Melatonin levels significantly improved in the active group compared to decreasing levels in the placebo group. The total sleep score assessed by the ISI improved significantly in the active group compared to placebo, resulting in higher sleep satisfaction, daily functioning and quality of life in the active group. Medicinal cannabis improved sleep time by an average of 30 minutes per night as well as quality of sleep compared to placebo. Furthermore, the active group felt significantly more clear-headed and more tranquil after the intervention compared to placebo.

We expect the peer-reviewed article be released April 2022.

Entoura anxiety and PTSD study

Together with Applied Cannabis Research, Entoura is currently recruiting for a research study investigating the effects and safety of medical cannabis on anxiety and PTSD as part of CACOS, the CA Clinics Observational Study.

This study collects and analyses data on medicinal cannabis for a range of hard-to-treat conditions through a series of surveys which record a patient’s treatment progress throughout a 12 month period, reporting on side effects, dosage and treatment satisfaction. Anecdotal and some clinical research support the use of cannabis medicines in mental health presentations, and Entoura’s study hopes to reveal further details on how effective medical cannabis is at reducing symptoms and improving quality of life.

Our friends at CA Clinics and Applied Cannabis Research are conducting a number of other studies that complement our initiatives at Entoura. By examining patient-reported outcomes for conditions related to pain, inflammation, sleep, palliative care as well as neurological, psychiatric, gastrointestinal and musculoskeletal disorder, the global medical cannabis community can learn from high-quality Australian research.

For more information, please contact Entoura.

https://www.entoura.com.au

自19世纪中期关于医用大麻的第一批科学报告问世以来，关于医用大麻的研究已成倍地增长。Pubmed已经发表了超过35000份大麻研究或研究报告，其中在过去10年里发表了超过19000份。

医用大麻在人类历史中的存在已超过一万年。对研究人员来说，将其历史应用转化为现代科学范式是一个不断发展的挑战。

作为一种具有广泛且可作药用的植物性药物，在大多数药物评估的受控条件下很难进行研究。近代史上的禁用和污名化进一步阻碍了大麻研究的进展。

然而，随着我们越来越了解特定大麻素的作用，随着世界各地耻辱和非法的外衣终于被揭开，像Entoura的那些精心设计的临床研究倡议，能以越来越大的信心评估医用大麻的益处。

药用大麻的古老用途

第一次将大麻作为药物使用的记录源于中国古代医学。中国医学文献记载，大麻被用于治疗痛风、消化不良和风湿病。

源自印度的吠陀文献记载了它在治疗睡眠障碍、焦虑、癫痫和发烧的用途。据记载，古埃及人使用药用大麻制剂治疗胃肠道症状、肿瘤和一系列疼痛症状——在现代医学中对应的是青光眼、月经疼痛和耳痛。

大麻在许多情况下已经被应用了几百年，甚至几千年，现在正被现代研究调查和验证。

大麻史

希腊和罗马人用大麻制剂治疗炎症和疼痛，在美洲，大麻常被用作止痛剂，治疗抽搐障碍和鸦片成瘾等。

在英国，17世纪著名的英国草药学家尼古拉斯·卡尔佩珀(Nicholas Culpepper)记录了使用医用大麻治疗关节疼痛、炎症、食欲、月经和消化问题的情况。

医用大麻科学研究的开端

从科学角度来看，第一次医用大麻的记录出现在19世纪中期。爱尔兰内科医生威廉·奥肖内西(William O 'Shaughnessy)博士是首批对大麻进行科学研究的人。

他的研究包括动物和人类的观察，在癫痫、风湿关节疼痛、姑息治疗和缓解霍乱呕吐等领域。

奥肖内西博士此后进行了其他研究，强调药用大麻作为镇静剂、止痛剂、睡眠障碍的使用，并发现它在某些心理演示中很有用。

医用大麻研究遭遇阻碍

进入20世纪，药用大麻治疗潜力的科学启蒙不仅没有加速，反而由于国际药物公约和围绕这种植物的种族主义政治漩涡(主要源于美国)，导致了医用大麻研究进展低迷。

可喜的是，还是有一些显著的突破。虽然大麻素CBD在1940年就被发现了，但THC在1964年被以色列研究人员Raphael Mechoulam和Yeheil Gaoni发现，这被证明是现代医用大麻研究的坚实基础。

如今著名的“大麻之祖”Mechoulam教授是内源性大麻素系统研究的先驱者。内源性大麻素系统是人体固有的大麻素系统，对免疫系统、激素和睡眠模式、食欲、情绪等都有影响。

这一发现促进了我们对这一以前未知的调节系统在体内的不同作用的理解，以及医用大麻如何发挥其治疗作用。

然而，这些最初的进步被禁酒令时代所扼杀，早在1906年，美国许多州就将大麻列为毒药。在20世纪大麻禁令期间，建立了现代临床研究的基础，包括随机对照试验和其他评估安全性和有效性的科学方法。但是，在这样一个科学进步的关键时期，由于受到地区和国际法规的限制，医用大麻被弃置一旁，无法进入现代医学研究结构。

在过去25年左右的时间里，大麻素领域的里程碑式发现以及世界各地禁烟期限制的缓慢解除，使得医用大麻研究变得越来越细致。从涉及大麻素或植物化学成分知之甚少的大麻制剂的试验，到如今对经过分析的大麻药物在特定条件下进行的临床试验。

20世纪90年代和21世纪初，大量研究在医用大麻如何利用于姑息治疗、多发性硬化症、癫痫和化疗引起的恶心和呕吐中发挥作用方面展开。

动物模型、人类细胞系和临床试验的研究继续揭示大麻素如何在肿瘤、焦虑、创伤后应激障碍、皮肤病、化疗引起的恶病质/厌食症和一系列自身免疫性疾病等领域发挥作用。

医用大麻研究中的知识产权挑战

医用大麻研究和产品开发面临的一个不能忽视的挑战是知识产权。作为一种历史悠久的以相对简单的剂型(酊剂或干花)使用的植物，药用大麻目前的大多数最终配方，很难产生IP。这打破了研究产品的传统途径，即IP带来研究机会和资金，通过临床试验将药物推向货架上的产品。

尽管很难获得知识产权，但在澳大利亚，大麻植物和产品在满足某些标准时，有资格获得一些知识产权保护，如专利和植物育种权。毫无疑问，随着越来越多的大麻许可证被授予和种植研究的扩大，我们可能会看到利用植物知识产权的临床研究进一步增加。

澳大利亚医用大麻研究

Entoura致力于医用大麻研究的进步和扩大病人获得大麻的机会。为实现这一目标，我们与其他著名的医用大麻公司进行合作，同时发起我们自己的临床试验，以增进全球对药用大麻的了解。

Entoura对医用大麻和睡眠的研究

对一些人来说，睡眠可能是一场美梦，对另一些人来说则是一场噩梦。医用大麻制剂已被证明对一些失眠患者的治疗作用。我们的睡眠研究旨在评估医用大麻对那些难以入睡或难以保持睡眠的人的安全性和有效性。

结果表明，Entoura EMC 10:15药用大麻油一般耐受性良好，并被发现在改善睡眠，褪黑激素水平和生活质量有效。

与安慰剂组的褪黑激素水平下降相比，活跃组的褪黑激素水平显著改善。与安慰剂组相比，ISI评估的总睡眠得分显著改善，活动组的睡眠满意度、日常功能和生活质量更高。与安慰剂相比，药用大麻每晚平均能提高30分钟的睡眠时间和睡眠质量。此外，与安慰剂组相比，活动组在干预后明显感觉头脑更清醒、更平静。

我们预计这篇经过同行评审的文章将于2022年4月发布。

对焦虑和创伤后应激障碍的研究

除了应用大麻研究，Entoura目前正在招募一项研究项目，研究医用大麻对焦虑和创伤后应激障碍的影响和安全性，这是CACOS, CA诊所观察研究的一部分。

本研究通过一系列调查，收集和分析关于药用大麻应用于一系列难以治疗的疾病的数据。这些调查记录了患者在12个月间的治疗进展，报告了副作用、剂量和治疗满意度。轶事和一些临床研究显示在心理健康介绍中使用大麻药物的益处，Entoura的研究希望进一步揭示医用大麻在减轻症状和提高生活质量方面的有效性的细节。

我们在CA诊所和应用大麻研究的同事在进行一些其他课题的研究，以补充我们在Entoura的倡议。通过检查患者报告的疼痛、炎症、睡眠、姑息治疗以及神经、精神、肠胃和肌肉骨骼疾病有关的情况的结果，全球医用大麻社区可以从澳大利亚的高质量研究中学习。

欲了解更多信息，请联系Entoura。

https://www.entoura.com.au