In The Netherlands, pharmaceutical-grade cultivated cannabis is distributed for medicinal purposes as commissioned by the Ministry of Health. Few studies have thus far described its therapeutic efficacy or subjective (adverse) effects in patients. The aims of this study are to assess the therapeutic satisfaction within a group of patients using prescribed pharmaceutical-grade cannabis and to compare the subjective effects among the available strains with special focus on their delta-9-tetrahydrocannabinol and cannabidiol content. In a cross-sectional and natural design, users of pharmaceutical-grade cannabis were investigated with questionnaires. Medical background of the patients was asked as well as experienced therapeutic effects and characteristics of cannabis use. Subjective effects were measured with psychometric scales and used to compare among the strains of cannabis used across this group of patients. One hundred two patients were included; their average age was 53 years and 76% used it for more than a year preceding this study. Chronic pain (53%; n = 54) was the most common medical indication for using cannabis followed by multiple sclerosis (23%; n = 23), and 86% (n = 88) of patients (almost) always experienced therapeutic satisfaction when using pharmaceutical cannabis. Dejection, anxiety, and appetite stimulation were found to differ among the 3 strains of cannabis. These results show that patients report therapeutic satisfaction with pharmaceutical cannabis, mainly pain alleviation. Some subjective effects were found to differ among the available strains of cannabis, which is discussed in relation to their different tetrahydrocannabinol/cannabidiol content. These results may aid in further research and critical appraisal for medicinally prescribed cannabis products.

It has become clear that the bronchial epithelium is not just a passive barrier but plays an active role in inflammation. It can produce several inflammatory mediators and does express cell adhesion molecules of which intercellular adhesion molecule (ICAM)-1 can be upregulated by cytokines like interferon (IFN)-gamma. In the present study, we analyzed in detail the interaction of neutrophils with human bronchial epithelial cells, both primary cultured cells and the bronchial epithelial cell line BEAS-2B. Confluent monolayers of epithelial cells were incubated with freshly isolated 51Cr-labeled neutrophils for 30 min at 37 degrees C; then the nonadherent cells were removed by washing gently. Stimulation of the epithelial cells with IFN-gamma or the combination of IFN-gamma and tumor necrosis factor-alpha (TNF-alpha) (which doubles the ICAM-1 expression) increased neutrophil adhesion. Activation of the neutrophils themselves with N-formylmethionyl-leucyl-phenylalanine (fMLP), platelet-activating factor, or TNF-alpha also caused a profound enhancement of the adhesion. A significant additional increase was found when the epithelial cells had been exposed to IFN-gamma and the neutrophils were stimulated with fMLP simultaneously. This effect was even more pronounced with epithelium preincubated with IFN-gamma and TNF-alpha. With the use of monoclonal antibodies against CD18 and ICAM-1, it was demonstrated that the increased adhesion was mainly mediated by the ICAM-1/beta 2-integrin interaction. This study highlights that both the activation state of the bronchial epithelial cells and the activation state of the neutrophils are critical for their interactive adhesion.

We studied the effect of the linoleic acid metabolite 13‐hydroxyoctadecadienoic acid (13‐HODE) on the increase of the intracellular calcium concentration, [Ca2+]i, induced by platelet‐activating factor (PAF), leukotriene B4 (LTB4), and formyl‐Met‐Leu‐Phe (fMLP) in human polymorphonuclear leukocytes (PMNs). 13‐HODE by itself did not change the [Ca2+]i of PMNs. However, when PMNs were preincubated with 13‐HODE and subsequently stimulated with PAF, LTB4, or fMLP, an inhibition of the increase of the [Ca2+]i was observed. The PAF‐induced calcium response was concentration‐dependently inhibited between 0.1 and 5 μM 13‐HODE. These results suggest that 13‐HODE can affect the increase of the [Ca2+]i and hence can modulate activation of PMNs. J. Leukoc. Biol. 56: 200–202; 1994.

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The effect of the linoleic acid metabolite 13-hydroxyoetadeeadienoie acid (13-HODE) on degranulation of human polymorphonuclear ieukocytes (PMNs) was investigated by measuring the expression of CDllb and CD67 on the plasma membrane. 13-HODE (5 pM) by itself induced degranulation of PMNs, but to a lesser extent as compared to PAF and fMLP. In addition, 13-HODE was found to inhibit the PAF-indueed degrannlation whereas an additive effect on the fMLP-induced PMNs degranulation was observed. These results indicate that 13-HODE can play a modulatory role in degranulation of PMNs.