title: Medicinal cannabis for neuropathic pain

authors: McKinnon, Marion

abstract: Neuropathic pain is caused by a dysfunction of the nervous system. It differs from normal pain sensations as it is no longer protective and can be present in the absence of a stimulus. It affects eight percent of the population worldwide and has several causes. Diabetes is the most prevalent cause, with about half of those diagnosed developing diabetic neuropathy. Other causes are genetic diseases (e.g. Charcot-Marie-Tooth disease), immune disorders or medications (e.g. chemotherapy drugs) or injury. Neuropathic pain, regardless of its cause, is often poorly managed leading to poor quality of life for those patients. The currently available analgesic options show little efficacy and are often dose-limiting due to adverse effects. Treatments that improve efficacy or offer lower adverse effects need to be investigated; one such potential treatment is medicinal cannabis. To this end, cannabis isolates and a high CBD whole extract were tested to determine efficacy to relieve neuropathic pain symptoms in a pre-clinical mouse model of neuropathy.
A dose-response trial using gene expression biomarkers was completed in wildtype mice. This was to determine what doses of orally administered CBD (25 - 150 mg/kg) in an olive oil vehicle had a biological effect in the dorsal root ganglia of peripheral nerves of mice. CBD (6.25 - 100 mg/kg), a high CBD whole extract (containing CBD 12.5 mg/kg and THC 0.867 mg/kg) and a pure CBD:THC mix (at the same concentrations) were then used to determine efficacy in ameliorating neuropathic pain in a CMT2A mouse model. Finally, a single high-dose streptozotocin-induced diabetic neuropathy mouse model was characterised to determine the parameters of peripheral neuropathy and neuropathic pain symptoms in male wildtype B6:D2 mice. 
A pure isolate of 12.5 mg/kg CBD showed the greatest efficacy in treating thermal hyperalgesia symptoms in CMT2A mice. This paralleled a clinically relevant dose of gabapentin (40mg/kg) in efficacy for improving thermal hyperalgesia, both as a single dose and in multiple doses across eight hours. Of the cannabinoids tested, high CBD whole extract showed greater efficacy in improving thermal hyperalgesia symptoms in CMT2A mice, with a wider therapeutic window than either CBD alone or CBD:THC. This indicates that in addition to THC, other components in cannabis may contribute to efficacy, or be the result of an entourage effect. 
Characterisation of the diabetic neuropathy model was completed, with two-thirds of the mice developing high blood glucose (≥ 17 mmol/L) within two weeks of a single high dose of streptozotocin. All diabetic mice showed thermal hyperalgesia symptoms and 40% of those also developed mechanical allodynia; with symptoms evident from as early as week four post- streptozotocin. There was no loss of motor function seen across the trial period of 13 weeks. Sciatic nerve tissue taken from these mice showed a marked loss of acetylated alpha-tubulin in both proximal and distal sciatic nerves when compared to the wildtype control group.

text: Medicinal cannabis for neuropathic pain Neuropathic pain is caused by a dysfunction of the nervous system. It differs from normal pain sensations as it is no longer protective and can be present in the absence of a stimulus. It affects eight percent of the population worldwide and has several causes. Diabetes is the most prevalent cause, with about half of those diagnosed developing diabetic neuropathy. Other causes are genetic diseases (e.g. Charcot-Marie-Tooth disease), immune disorders or medications (e.g. chemotherapy drugs) or injury. Neuropathic pain, regardless of its cause, is often poorly managed leading to poor quality of life for those patients. The currently available analgesic options show little efficacy and are often dose-limiting due to adverse effects. Treatments that improve efficacy or offer lower adverse effects need to be investigated; one such potential treatment is medicinal cannabis. To this end, cannabis isolates and a high CBD whole extract were tested to determine efficacy to relieve neuropathic pain symptoms in a pre-clinical mouse model of neuropathy.
A dose-response trial using gene expression biomarkers was completed in wildtype mice. This was to determine what doses of orally administered CBD (25 - 150 mg/kg) in an olive oil vehicle had a biological effect in the dorsal root ganglia of peripheral nerves of mice. CBD (6.25 - 100 mg/kg), a high CBD whole extract (containing CBD 12.5 mg/kg and THC 0.867 mg/kg) and a pure CBD:THC mix (at the same concentrations) were then used to determine efficacy in ameliorating neuropathic pain in a CMT2A mouse model. Finally, a single high-dose streptozotocin-induced diabetic neuropathy mouse model was characterised to determine the parameters of peripheral neuropathy and neuropathic pain symptoms in male wildtype B6:D2 mice. 
A pure isolate of 12.5 mg/kg CBD showed the greatest efficacy in treating thermal hyperalgesia symptoms in CMT2A mice. This paralleled a clinically relevant dose of gabapentin (40mg/kg) in efficacy for improving thermal hyperalgesia, both as a single dose and in multiple doses across eight hours. Of the cannabinoids tested, high CBD whole extract showed greater efficacy in improving thermal hyperalgesia symptoms in CMT2A mice, with a wider therapeutic window than either CBD alone or CBD:THC. This indicates that in addition to THC, other components in cannabis may contribute to efficacy, or be the result of an entourage effect. 
Characterisation of the diabetic neuropathy model was completed, with two-thirds of the mice developing high blood glucose (≥ 17 mmol/L) within two weeks of a single high dose of streptozotocin. All diabetic mice showed thermal hyperalgesia symptoms and 40% of those also developed mechanical allodynia; with symptoms evident from as early as week four post- streptozotocin. There was no loss of motor function seen across the trial period of 13 weeks. Sciatic nerve tissue taken from these mice showed a marked loss of acetylated alpha-tubulin in both proximal and distal sciatic nerves when compared to the wildtype control group.

year: 2024

title: Digital trust - trusted computing and beyond: A position paper

authors: Akram, Raja Naeem

subjects: Cloud computing

abstract: Along with the invention of computers and interconnected networks, physical societal notions like security, trust, and privacy entered the digital environment. The concept of digital environments begins with the trust (established in the real world) in the organisation/individual that manages the digital resources. This concept evolved to deal with the rapid growth of the Internet, where it became impractical for entities to have prior offline (real world) trust. The evolution of digital trust took diverse approaches and now trust is defined and understood differently across heterogeneous domains. This paper looks at digital trust from the point of view of security and examines how valid trust approaches from other domains are now making their way into secure computing. The paper also revisits and analyses the Trusted Platform Module (TPM) along with associated technologies and their relevance in the changing landscape. We especially focus on the domains of cloud computing, mobile computing and cyber-physical systems. In addition, the paper also explores our proposals that are competing with and extending the traditional functionality of TPM specifications.

text: Digital trust - trusted computing and beyond: A position paper Along with the invention of computers and interconnected networks, physical societal notions like security, trust, and privacy entered the digital environment. The concept of digital environments begins with the trust (established in the real world) in the organisation/individual that manages the digital resources. This concept evolved to deal with the rapid growth of the Internet, where it became impractical for entities to have prior offline (real world) trust. The evolution of digital trust took diverse approaches and now trust is defined and understood differently across heterogeneous domains. This paper looks at digital trust from the point of view of security and examines how valid trust approaches from other domains are now making their way into secure computing. The paper also revisits and analyses the Trusted Platform Module (TPM) along with associated technologies and their relevance in the changing landscape. We especially focus on the domains of cloud computing, mobile computing and cyber-physical systems. In addition, the paper also explores our proposals that are competing with and extending the traditional functionality of TPM specifications.

year: 2015-01-15

title: Section 2: Native disruption: Maori and the precariat: Introduction

authors: Masters-Awatere, Bridgette

abstract: Within this section, the authors encourage the reader to look back into history and then consider the future. We are invited to re-examine deeds from this country’s past. To immerse ourselves in a narrative that may be different to the one we have been taught in school, or heard among our friends and family. Through their stories we can see multiple narratives. Readers are invited to understand, embrace and own the past. By recognising and accepting the past — our collective histories — we can determine our collective present and future.

text: Section 2: Native disruption: Maori and the precariat: Introduction Within this section, the authors encourage the reader to look back into history and then consider the future. We are invited to re-examine deeds from this country’s past. To immerse ourselves in a narrative that may be different to the one we have been taught in school, or heard among our friends and family. Through their stories we can see multiple narratives. Readers are invited to understand, embrace and own the past. By recognising and accepting the past — our collective histories — we can determine our collective present and future.

year: 2017